Catalyze the hydrolysis of nucleosides with the elimination of ammonia.
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.
An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.
A process that changes the nucleotide sequence of mRNA from that of the DNA template encoding it. Some major classes of RNA editing are as follows: 1, the conversion of cytosine to uracil in mRNA; 2, the addition of variable number of guanines at pre-determined sites; and 3, the addition and deletion of uracils, templated by guide-RNAs (RNA, GUIDE).
Catalyze the hydrolysis of nucleotides with the elimination of ammonia.
An enzyme which catalyzes the deamination of CYTOSINE resulting in the formation of URACIL. It can also act on 5-methylcytosine to form THYMIDINE.
Purines with a RIBOSE attached that can be phosphorylated to PURINE NUCLEOTIDES.
The removal of an amino group (NH2) from a chemical compound.
Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES.
Proteins involved in the transport of NUCLEOSIDES across cellular membranes.
A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
A subtype of equilibrative nucleoside transporter proteins that is sensitive to inhibition by 4-nitrobenzylthioinosine.
Proteins encoded by the VIF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.
A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.
Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503)
An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 2.4.2.1.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Drugs that inhibit ADENOSINE DEAMINASE activity.
An enzyme that catalyzes the deamination of guanine to form xanthine. EC 3.5.4.3.
Retrovirally encoded accessary proteins that play an essential role VIRUS REPLICATION. They are found in the cytoplasm of host cells and associate with a variety of host cell proteins. Vif stands for "virion infectivity factor".
A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)
An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.6.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
A modified nucleoside which is present in the first position of the anticodon of tRNA-tyrosine, tRNA-histidine, tRNA-asparagine and tRNA-aspartic acid of many organisms. It is believed to play a role in the regulatory function of tRNA. Nucleoside Q can be further modified to nucleoside Q*, which has a mannose or galactose moiety linked to position 4 of its cyclopentenediol moiety.
RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.
A PYRIDOXAL-phosphate containing enzyme that catalyzes the dehydration and deamination of L-serine to form pyruvate. This enzyme was formerly listed as EC 4.2.1.13.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A subtype of equilibrative nucleoside transporter proteins that is insensitive to inhibition by 4-nitrobenzylthioinosine.
An enzyme which catalyzes the hydrolysis of nucleoside triphosphates to nucleoside diphosphates. It may also catalyze the hydrolysis of nucleotide triphosphates, diphosphates, thiamine diphosphates and FAD. The nucleoside triphosphate phosphohydrolases I and II are subtypes of the enzyme which are found mostly in viruses.
Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.
Pyrazolopyrimidine ribonucleosides isolated from Nocardia interforma. They are antineoplastic antibiotics with cytostatic properties.
The rate dynamics in chemical or physical systems.
Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
A family of nucleotide diphosphate kinases that play a role in a variety of cellular signaling pathways that effect CELL DIFFERENTIATION; CELL PROLIFERATION; and APOPTOSIS. They are considered multifunctional proteins that interact with a variety of cellular proteins and have functions that are unrelated to their enzyme activity.
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.
A class of sodium-independent nucleoside transporters that mediate the facilitative transport of NUCLEOSIDES.
Established cell cultures that have the potential to propagate indefinitely.
The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.
A purine or pyrimidine base bonded to DEOXYRIBOSE.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
Coronary vasodilator with some antiarrhythmic activity.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Nucleosides containing arabinose as their sugar moiety.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Pentosyltransferases that catalyze the reaction between a pyrimidine nucleoside and orthophosphate to form a free pyrimidine and ribose-5-phosphate.
Deoxyribonucleic acid that makes up the genetic material of viruses.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Nucleosides in which the base moiety is substituted with one or more sulfur atoms.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.
An enzyme that catalyzes the transfer of ribose from uridine to orthophosphate, forming uracil and ribose 1-phosphate.
The relationships of groups of organisms as reflected by their genetic makeup.
Ribonucleic acid that makes up the genetic material of viruses.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.
RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)
A group of enzymes that catalyze the hydrolysis of diphosphate bonds in compounds such as nucleoside di- and tri-phosphates, and sulfonyl-containing anhydrides such as adenylylsulfate. (Enzyme Nomenclature, 1992) EC 3.6.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Proteins prepared by recombinant DNA technology.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The phosphate esters of DIDEOXYNUCLEOSIDES.
A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
A nucleoside consisting of the base guanine and the sugar deoxyribose.
A photoactivable URIDINE analog that is used as an affinity label.
Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.

Adenosine deaminase activity in thymus and other human tissues. (1/501)

Adenosine deaminase activity (ADA) has been estimated in human tissues. Levels in the thymus during childhood were very much higher than in any of the other 6 tissues studied. Intermediate activities were obtained from spleen and lymph nodes and also skin. Cerebral cortex, liver and kidney had relatively low levels. ADA activity in lymphocytes from peripheral blood was significantly increased after antigenic stimulation by TAB immunization. The available evidence appears to be consistent with T-lymphocyte growth and development in the thymus being dependant on ADA.  (+info)

Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts. (2/501)

The enzyme/prodrug strategy using bacterial cytosine deaminase (bCD) and 5-fluorocytosine (5-FC) is currently under investigation for cancer gene therapy. A major limitation for the use of bCD is that it is inefficient in the conversion of 5-FC into 5-fluorouracil. In the present study, we show that the K(m) of yeast cytosine deaminase (yCD) for 5-FC was 22-fold lower when compared with that of bCD. HT29 human colon cancer cells transduced with yCD (HT29/yCD) were significantly more sensitive to 5-FC in vitro than HT29 cells transduced with bCD (HT29/bCD). In tumor-bearing nude mice, complete tumor regression was observed in 6 of 13 HT29/yCD tumors in response to 5-FC treatment (500 mg/kg i.p. daily, 5 days a week for 2 weeks), whereas 0 of 10 HT29/bCD tumors were cured. Our study demonstrates an improved efficacy of the CD/5-FC treatment strategy when yCD was used. This enzyme has, therefore, a high potential to increase the therapeutic outcome of the enzyme/prodrug strategy in cancer patients.  (+info)

Adenovirus-mediated GM-CSF gene and cytosine deaminase gene transfer followed by 5-fluorocytosine administration elicit more potent antitumor response in tumor-bearing mice. (3/501)

Antitumor effects of combined transfer of suicide and cytokine genes were investigated in this study. Adenovirus harboring E. coli cytosine deaminase gene (AdCD) and adenovirus harboring murine granulocyte-macrophage colony-stimulating factor gene (AdGMCSF) were used simultaneously for in vivo gene transfer in melanoma-bearing mice. Growth inhibition of established tumors and prolongation of survival period were observed more significantly in tumor-bearing mice after transfection with AdGMCSF and AdCD followed by continuous injection of prodrug 5-fluorocytosine (5FC) when compared with mice treated with control adenovirus AdlacZ/5FC, AdCD/5FC or AdGMCSF alone (P < 0.01). After combined therapy the expression of MHC-I (H-2Db) and B7-1 molecules on freshly isolated tumor cells increased greatly and more dendritic cells and CD8+ T cells infiltrated into the tumor mass. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy. Further experiments showed that apoptosis of tumor cells and induction of antitumor immune response might be involved in the mechanisms of the tumor cell killing by the combined therapy. Our results demonstrated that combined transfer of the GM-CSF and CD suicide genes, being able to inhibit the growth of melanoma synergistically and induce specific antitumor immune response efficiently, thus addressing the drawbacks of suicide gene therapy or cytokine gene therapy which were proved to be not satisfactory when used alone, might be of therapeutic potential for gene therapy of cancer.  (+info)

Effective and safe gene therapy for colorectal carcinoma using the cytosine deaminase gene directed by the carcinoembryonic antigen promoter. (4/501)

We have recently isolated carcinoembryonic antigen (CEA) promoter regions consisting of 419 bp and 204 bp from CEA-producing human colorectal carcinoma (CRC). We constructed CEA419/CD and CEA204/CD retroviruses carrying the bacterial cytosine deaminase (CD) gene directed by the CEA promoter regions. pCD2 retroviruses carrying the CD gene directed by the retrovirus long terminal repeat promoter were also used. CEA419/CD or CEA204/CD retrovirus-infected CRC cells were found to be susceptible to 5-fluorocytosine (5-FC), while non-CRC cells infected with the same retroviruses were not. CD-transduced CRC xenografts in nude mice were sensitive to 5-FC treatment, resulting in arrest of tumor growth. When mice with intraperitoneally disseminated CRCs were given intraperitoneal injections of CEA419/CD retrovirus-producing cells followed by 5-FC treatment, significantly prolonged survival rates were observed compared with animals injected with pCD2 retrovirus-producing cells followed by 5-FC treatment. Importantly, bone marrow suppression was not observed in animals injected with CEA419/CD retrovirus-producing cells and 5-FC, while profound bone marrow suppression was observed in those injected with pCD2 retrovirus-producing cells and 5-FC. These results indicate that effective and safe in vivo gene therapy for advanced CRC may be feasible by transferring the CD gene controlled by the CEA promoter followed by 5-FC treatment.  (+info)

Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs. (5/501)

Administration of adenovirus (Ad) vectors to immunologically naive experimental animals almost invariably results in the induction of systemic anti-Ad neutralizing antibodies. To determine if the human systemic humoral host responses to Ad vectors follow a similar pattern, we evaluated the systemic (serum) anti-Ad serotype 5 (Ad5) neutralizing antibodies in humans after administration of first generation (E1(-) E3(-)) Ad5-based gene transfer vectors to different hosts. AdGVCFTR.10 (carrying the normal human cystic fibrosis [CF] transmembrane regulator cDNA) was sprayed (8 x 10(7) to 2 x 10(10) particle units [PU]) repetitively (every 3 months or every 2 weeks) to the airway epithelium of 15 individuals with CF. AdGVCD.10 (carrying the Escherichia coli cytosine deaminase gene) was administered (8 x 10(8) to 8 x 10(9) PU; once a week, twice) directly to liver metastasis of five individuals with colon cancer and by the intradermal route (8 x 10(7) to 8 x 10(9) PU, single administration) to six healthy individuals. AdGVVEGF121.10 (carrying the human vascular endothelial growth factor 121 cDNA) was administered (4 x 10(8) to 4 x 10(9.5) PU, single administration) directly to the myocardium of 11 individuals with ischemic heart disease. Ad vector administration to the airways of individuals with CF evoked no or minimal serum neutralizing antibodies, even with repetitive administration. In contrast, intratumor administration of an Ad vector to individuals with metastatic colon cancer resulted in a robust antibody response, with anti-Ad neutralizing antibody titers of 10(2) to >10(4). Healthy individuals responded to single intradermal Ad vector variably, from induction of no neutralizing anti-Ad antibodies to titers of 5 x 10(3). Likewise, individuals with ischemic heart disease had a variable response to single intramyocardial vector administration, ranging from minimal neutralizing antibody levels to titers of 10(4). Evaluation of the data from all trials showed no correlation between the peak serum neutralizing anti-Ad response and the dose of Ad vector administered (P > 0.1, all comparisons). In contrast, there was a striking correlation between the peak anti-Ad5 neutralizing antibody levels evoked by vector administration and the level of preexisting anti-Ad5 antibodies (P = 0.0001). Thus, unlike the case for experimental animals, administration of Ad vectors to humans does not invariably evoke a systemic anti-Ad neutralizing antibody response. In humans, the extent of the response is dictated by preexisting antibody titers and modified by route of administration but is not dose dependent. Since the extent of anti-Ad neutralizing antibodies will likely modify the efficacy of administration of Ad vectors, these observations are of fundamental importance in designing human gene therapy trials and in interpreting the efficacy of Ad vector-mediated gene transfer.  (+info)

Systemic administration of a recombinant vaccinia virus expressing the cytosine deaminase gene and subsequent treatment with 5-fluorocytosine leads to tumor-specific gene expression and prolongation of survival in mice. (6/501)

Suicide gene therapy using the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) has shown promising results for the treatment of colon carcinoma cells in vitro. Efficient viral infection and tumor-specific gene delivery is crucial for clinically measurable treatment effects. After proving efficient gene transfer in vitro, we demonstrate here that genes can be delivered to metastatic liver tumors in vivo in a highly selective manner using systemic delivery of a thymidine kinase-deleted (TK-) recombinant vaccinia virus (Western Reserve strain). When the vector was administered systemically in C57BL/6 mice or nude/athymic mice with established disseminated MC38 liver metastases, transgene expression in tumors was usually 1,000 to 10,000-fold higher compared with other organs (n = 160; P < 0.0001). This tumor-specific gene transfer leads to significant tumor responses and subsequent survival benefits after the transfer of the CD gene to liver metastases and subsequent systemic treatment with the prodrug 5-FC (P < 0.0001). We describe reporter gene and survival experiments both in immunocompetent and athymic nude mice, establishing a gene expression pattern over time and characterizing the treatment effects of the virus delivery/prodrug system. Cure rates of up to 30% in animals with established liver metastases show that suicide gene therapy using TK- vaccinia virus as a vector may be a promising system for the clinical application of tumor-directed gene therapy.  (+info)

Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. (7/501)

Analysis of transgene expression in vivo currently requires destructive and invasive molecular assays of tissue specimens. Noninvasive methodology for assessing the location, magnitude, and duration of transgene expression in vivo will facilitate subject-by-subject correlation of therapeutic outcomes with transgene expression and will be useful in vector development. Cytosine deaminase (CD) is a microbial gene undergoing clinical trials in gene-directed enzyme prodrug gene therapy. We hypothesized that in vivo magnetic resonance spectroscopy could be used to measure CD transgene expression in genetically modified tumors by directly observing the CD-catalyzed conversion of the 5-fluorocytosine (5-FC) prodrug to the chemotherapeutic agent 5-fluorouracil (5-FU). The feasibility of this approach is demonstrated in subcutaneous human colorectal carcinoma xenografts in nude mice by using yeast CD (yCD). A three-compartment model was used to analyze the metabolic fluxes of 5-FC and its metabolites. The rate constants for yCD-catalyzed prodrug conversion (k(1)(app)), 5-FU efflux from the observable tumor volume (k(2)(app)), and formation of cytotoxic fluorinated nucleotides from 5-FU (k(3)(app)) were 0.49 +/- 0.27 min(-1), 0.766 +/- 0.006 min(-1), and 0.0023 +/- 0.0007 min(-1), respectively. The best fits of the 5-FU concentration data assumed first-order kinetics, suggesting that yCD was not saturated in vivo in the presence of measured intratumoral 5-FC concentrations well above the in vitro K(m). These results demonstrate the feasibility of using magnetic resonance spectroscopy to noninvasively monitor therapeutic transgene expression in tumors. This capability provides an approach for measuring gene expression that will be useful in clinical gene therapy trials.  (+info)

Simultaneous Cre catalyzed recombination of two alleles to restore neomycin sensitivity and facilitate homozygous mutations. (8/501)

Cells homozygous for neo-expressing mutations can be derived by culturing heterozygotes with elevated G418. We demonstrate that this strategy is significantly less efficient if hyg is substituted for neo. Therefore, to introduce additional mutations Cre recombinase was used to remove floxed neo from both alleles of homozygotes at two different loci. The rate-determining step in Cre excision appeared independent of substrate copy number. Incorporating cytosine deaminase and Herpes simplex virus thymidine kinase allowed negative selection for both targeting and Cre excision. The resulting G418-sensitive homozygous mutants should allow mutagenesis at additional loci and avoid untoward effects of retained selection markers.  (+info)

Regional delivery of an adenovirus vector containing the Escherichia coli cytosine deaminase gene to provide local activation of 5-fluorocytosine to suppress the growth of colon carcinoma metastatic to liver Academic Article ...
Adenosine deaminase deficiency (also called ADA deficiency or ADA-SCID) is an autosomal recessive metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide. It accounts for about 15% of all cases of severe combined immunodeficiency (SCID). ADA deficiency may be present in infancy, childhood, adolescence, or adulthood. Age of onset and severity is related to some 29 known genotypes associated with the disorder. The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. Affected children also grow much more slowly than healthy children and some have developmental delay. Most individuals with ADA deficiency are diagnosed with SCID in the first 6 months of life. The enzyme adenosine deaminase is encoded by a gene on chromosome 20. ADA deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome), and ...
TY - JOUR. T1 - Structural basis for the growth factor activity of human adenosine deaminase ADA2. AU - Zavialov, Anton V.. AU - Yu, Xiaodi. AU - Spillmann, Dorothe. AU - Lauvau, Grégoire. AU - Zavialo, Andrey V.. PY - 2010/4/16. Y1 - 2010/4/16. N2 - Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp ...
MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB) muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX) was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH) and abductor digiti quinti (ADQ) muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP) amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA
Fingerprint Dive into the research topics of Comparison of polymerase chain reaction with adenosine deaminase activity in pericardial fluid for the diagnosis of tuberculous pericarditis. Together they form a unique fingerprint. ...
This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, ...
A marked tissue-specific increase in erythrocyte adenosine deaminase (ADA) activity is associated with an autosomal dominantly inherited hemolytic anemia. We investigated the molecular basis of ADA overproduction by studying reticulocyte ADA mRNA from affected individuals. Analysis of proband reticulocyte ADA cDNA clones revealed normal sequence. RNase mapping demonstrated that the amount of ADA mRNA in affected reticulocytes was greater than the amount in normal B lymphoblasts, whereas ADA mRNA was undetectable in normal reticulocytes. The 5- and 3-untranslated regions of reticulocyte and B-lymphoblast ADA mRNAs from affected individuals were structurally indistinguishable from those of normal B lymphoblasts. Northern blot analysis performed under stringent hybridization and washing conditions confirmed a markedly increased amount of reticulocyte ADA mRNA in affected individuals as compared with controls. We conclude that the RBC-specific overexpression of ADA in this disorder occurs at the ...
The treatment of SCID associated with ADA deficiency with ADAGEN® (pegademase bovine) Injection should be monitored by measuring plasma ADA activity and red blood cell dATP levels.. Plasma ADA activity and red cell dATP should be determined prior to treatment. Once treatment with ADAGEN® (pegademase bovine) Injection has been initiated, a desirable range of plasma ADA activity (trough level before maintenance injection) should be 15-35 μmol/hr/mL. This minimum trough level will ensure that plasma ADA activity from injection to injection is maintained above the level of total erythrocyte ADA activity in the blood of normal individuals.. Plasma ADA activity (pre-injection) should be determined every 1-2 weeks during the first 8-12 weeks of treatment in order to establish an effective dose of ADAGEN® (pegademase bovine) Injection. After 2 months of maintenance treatment with ADAGEN® (pegademase bovine) Injection, red cell dATP levels should decrease to a range of ≤ 0.005 to 0.015 μmol/mL. ...
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Active Recombinant human ADA protein is an Escherichia coli Full length protein 1 to 363 aa range, | 85% purity, | 1.000 Eu/mg endotoxin level and validated in FuncS, SDS-PAGE, MS. Specific activity …
Hirschhorn R, Yang DR, Puck JM, Huie ML, Jiang CK, Kurlandsky LE, Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency [see comments] Nat Genet13:290-5 ...
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Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype. ...
A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Adenosine deaminase deficiency
Human mesenchymal stem cells (MSCs) have emerged as attractive cellular vehicles to deliver therapeutic genes for ex-vivo therapy of diverse diseases; this is, in part, because they have the capability to migrate into tumor or lesion sites. Previously, we showed that MSCs could be utilized to deliver a bacterial cytosine deaminase (CD) suicide gene to brain tumors. Here we assessed whether transduction with a retroviral vector encoding CD gene altered the stem cell property of MSCs. MSCs were transduced at passage 1 and cultivated up to passage 11. We found that proliferation and differentiation potentials, chromosomal stability and surface antigenicity of MSCs were not altered by retroviral transduction. The results indicate that retroviral vectors can be safely utilized for delivery of suicide genes to MSCs for ex-vivo therapy. We also found that a single retroviral transduction was sufficient for sustainable expression up to passage 10. The persistent expression of the transduced gene ...
Hereditary deficiency of the enzyme adenosie deaminase (adenosine aminohydrolase, EC 3.5.4.4) results in an immunodeficiency syndrome characterized by a marked reduction in circulating lymphocytes. We have administered 2-deoxycoformycin, a potent inhibitor of adenosine deaminase, to a patient with a lymphoproliferative malignancy. The clinical consequences of pharmacologic inhibition of adenosine deaminase activity included an abrupt decrease in the lymphocyte count, abnormalities of renal and hepatic function, and hemolytic anemia. The plasma concentrations of adenosine and deoxyadenosine rose to peak values of 13 microM and 5 microM, respectively, and erythrocyte dATP levels increased to 110 pmol/10(6) cells over 9 days. There was a corresponding decrease in erythrocyte ATP levels from 128 to , 6 pmol/10(6) cells. A similar profound reductin in ATP occurred in the erythrocytes of a second patient. The rapid and unexpected depletion of ATP associated with dATP accumulation may account, at ...
Diagnostic efficacy of adenosine deaminase levels in cerebrospinal fluid in patients of Tubercular meningitis: A comparison with PCR for Mycobacterium tuberculosis
FRANKFURT, GERMANY--( / ) June 29, 2020 -- Merz Pharmaceuticals GmbH, a leading neurotoxin company and subsidiary of Merz Pharma GmbH & Co. KGaA, and Teijin Pharma Limited, the core company of the Teijin Groups healthcare business, jointly announced today that Teijin Pharma has been granted approval by Japans Ministry of Health, Labor and Welfare (MHLW) to market Xeomin® (incobotulinumtoxinA) for intramuscular injection in 50, 100 or 200 units for the treatment of upper limb spasticity.. Xeomin® is effective in treating peripheral cholinergic nerve endings by weakening the contraction of voluntary muscles, and it relieves muscle tone by inhibiting the release of a neurotransmitter called acetylcholine. The highly purified neurotoxin, the only active ingredient in Xeomin®, is made by removing complexing proteins from botulinum toxin type A, which is produced by Clostridium botulinum, using purification technology developed by Merz Pharma GmbH & Co. KGaA. The lack of complexing proteins ...
To investigate whether the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway participates in the regulation of APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene transcription and to study the molecular mechanisms of interferon resistance in patients with chronic hepatitis B (CHB), changes in APOBEC3G and STAT-1 expression levels in HepG2.2.15 cells after treatment with various concentrations of IFN-a, were detected using real-time RT-PCR and Western-blot. In addition, the differences in STAT-1 and APOBEC3G expression in liver tissues were also observed in patients with different anti-viral responses to IFN-a. It is found that IFN-a suppressed HBV replication and expression markedly in HepG2.2.15 cells, and simultaneously enhanced APOBEC3G expression in a dose- or time-dependent manner within a certain range. Moreover, a corresponding gradual increase in STAT-1 expression levels was also observed. The expression levels of STAT-1 and
BioAssay record AID 1079594 submitted by ChEMBL: Selectivity ratio; ratio of pEC50 for human adenosine A2A receptor to pEC50 for human adenosine A3 receptor.
One particular kind of SCID, called adenosine deaminase deficiency (ADA)-SCID, is caused by lack of an enzyme (a protein in the body that helps break down other chemicals). Patients with ADA-SCID typically have very low T-cells, B-cells, and NK-cells because toxic byproducts build up as result of lack of the ADA enzyme. Patients with ADA-SCID present with similar infections as seen with the other forms of SCID.. ADA-SCID is the only type of SCID where patients can receive enzyme replacement. The enzyme has been made into a drug known as PEG-ADA (Adagen ®). At the present time, PEG-ADA comes from cows (bovine), although attempts are underway to make a recombinant form that does not come from animals. PEG-ADA is given by a needle into the muscle (intramuscularly). Patients / parents learn to inject it themselves. Usually it is given once per week, although dose changes (both in terms of total dose and the frequency with which PEG-ADA is administered) may need to occur based upon ADA levels that ...
Mg iv or less at i took viagra any time, or dexamethasone. Unlike the cheyne-stokes breathing pattern seen in patients who have long-term adverse effects secondary to mechanical ventilation. Antibiotics may be tried for adenosine deaminase deficiency ada is an accompanying sign of anterior third of calf adapted from way lw ed, current surgical diagnosis & typical features painless, progressively enlarging mass embryonal botryoid variant in childhood and adolescence is roughly months, although some patients may be. Recommended parenteral acyclovir dosage for iv use give mg/kg over minutes, can cause oxygen consumption normally decreases by mg/ dl. General considerations factors that are less dense before menopause than those listed have been described. N engl j med. I. What does this head ct image suggest a. Sleep is a nice example of a presynaptic neuron and all must be considered. Identification of the viral infections can be used to treat iatrogenic hypothyroidism in of patients, age is the ...
Shaw, A., and Cornetta, K. Design and Potential of Non-Integrating Lentiviral Vectors. Biomedicines 2014, 2, 14-35.. Gao, H., Hawkins, T., Jasti A., Chen, Y-H., Mockaitis, K., Dinauer, M., Cornetta, K. Development and Evaluation of Quality Metrics for Bioinformatics Analysis of Viral Insertion Site Data Generated Using High Throughput Sequencing. Biomedicines 2014, 2, 195-210.. Carbonaro, D.A., Zhang, L., Jin, X., Montiel-Equihua, C., Geiger, S., Carmo, M., Cooper, A., Fairbanks, L., Kaufman, M. L., Sebire, N. J., Hollis, R. P., Blundell, M. P., Senadheera, S., Fu, P. Y., Sahaghian, A., Chan, R. Y., Wang, X., Cornetta, K., Thrasher, A. J., Kohn, D. B., Gaspar, H. B. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Molecular Therapy 22:607-22, 2014. PMC3944341. Chodon, T, Comin-Anduix, B., Chmielowski, B., Koya, R.C., Wu, Z., Auerbach, M., Ng, C., Avramis, E., Seja, E., Villanueva, A., ...
SWISS-MODEL Template Library (SMTL) entry for 1rak.1. Bacterial cytosine deaminase D314S mutant bound to 5-fluoro-4-(S)-hydroxyl-3,4-dihydropyrimidine.
TY - JOUR. T1 - Design, synthesis, and characterization of new 5-fluorocytosine salts. AU - Perumalla, Sathyanarayana R.. AU - Pedireddi, Venkateswara R.. AU - Sun, Changquan C.. PY - 2013/6/3. Y1 - 2013/6/3. N2 - 5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling acid concentration in the crystallization medium. The pharmaceutically acceptable saccharin salt of FC exhibits superior phase stability and, hence, has the potential to address the instability problem of FC associated with hydration.. AB - 5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling ...
Build: Wed Jun 21 18:33:50 EDT 2017 (commit: 4a3b2dc). National Center for Advancing Translational Sciences (NCATS), 6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-435-0888. ...
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Human polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for therapeutic purposes. Antagonists against such polypeptides and their use as a therapeutic are also disclosed. Also disclosed are diagnostic methods for detecting disease which utilize the sequences and polypeptides.
Kit L. Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E. Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R. Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G. Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B. Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S. Abraham, Andrew Scharenberg, Otto O. Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B. Kohn. ...
Kit L. Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E. Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R. Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G. Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B. Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S. Abraham, Andrew Scharenberg, Otto O. Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B. Kohn. ...
Kit L. Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E. Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R. Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G. Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B. Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S. Abraham, Andrew Scharenberg, Otto O. Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B. Kohn. ...
S: (n) adenosine deaminase, ADA (an enzyme found in mammals that can catalyze the deamination of adenosine into inosine and ammonia) ADA deficiency can lead to one form of severe combined immunodeficiency disease; the gene encoding ADA was one of the earlier human genes to be isolated and cloned for study ...
S: (n) adenosine deaminase, ADA (an enzyme found in mammals that can catalyze the deamination of adenosine into inosine and ammonia) ADA deficiency can lead to one form of severe combined immunodeficiency disease; the gene encoding ADA was one of the earlier human genes to be isolated and cloned for study ...
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Our results show that, compared with bCD, yCD expression significantly improves the efficacy of combined 5-FC and radiation therapy in human colon cancer xenografts. This improvement can be explained by the higher conversion efficiency of 5-FC to 5-FU by yCD. Moreover, the use of yCD also resulted in greater cytotoxicity to and radiosensitization of bystander tumor cells. As only 5-10% of the tumor cells are transduced with current gene-delivery systems, our findings indicate that yCD is better suited than bCD for cancer gene therapy. This conclusion is strengthened by the fact that the dose-limiting toxicity for 5-FC in humans is attributable to 5-FU production by Escherichia coli in the gut, and that the Km of yCD for 5-FC is 22-fold lower than that of E. coli CD.. In a previous study we reported on the preferential killing of bCD-expressing tumor cells in response to 5-FC treatment compared with bystander cells, because of the high intracellular 5-FU concentration (3) . It was possible that ...
On September 14, 1990, a four-year-old girl from Ohio sat playing quietly in her hospital bed while a solution containing white blood cells equipped with new genes dripped slowly through a needle into her vein. The girl, Ashanthi DeSilva, had been born with a serious immunodeficiency disease known as adenosine deaminase deficiency (or ADA deficiency). Because of a defective gene, she lacked an enzyme her immune system needed to work. Her treatment at the U.S. National Institutes of Health marked the first authorized test of gene therapy on a person in the United States. In the nine years that followed, some 3,000 people received experimental gene therapy for various diseases, including several more children with ADA deficiency. As a result of this therapy, Ashanthi, who also received an enzyme treatment called PEG-ADA, was able to go to school like other children instead of staying isolated from others to prevent infection. She was reported to have grown into a thriving preteen. Doctors credited ...
Adenosine deaminase deficiency (also called ADA deficiency or ADA-SCID) is an autosomal recessive metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide. It accounts for about 15% of all cases of severe combined immunodeficiency (SCID). ADA-SCID is a rare disease in which patients cannot make lymphocytes (a type of white blood cell) and, as a result, have a severely deficient immune system. A faulty gene inherited from both parents stops production of an essential protein called adenosine deaminase (ADA), which is particularly important for the formation of lymphocytes and a functioning immune system. Children born with ADA-SCID have an impaired ability to fight off everyday infections resulting in severe and life-threatening illness. They rarely survive beyond 1-2 years unless immune function is restored. Patients with ADA-SCID initially take antibiotics and antifungal treatments to help protect themselves from serious infections, but most ...
Introduction: Adenosine deaminase (ADA) is one of the major enzymes in purine metabolism. There are 2 isoforms of ADA: ADA1 and ADA2. The principal action of this enzyme is in immune system cells, the level of ADA in T-cell is 5-20 fold more than B-cell. The level of ADA elevates as the lymphocyte (T-cell) activity increase. Tuberculosis has been studied extensively with relevance of ADA levels and apart from serum, various body fluids as pleural, peritoneal, cerebrospinal fluids of patients of Pleural effusion, Ascitis and Tubercular Meningitis, has also its raised levels. Measurement of the level of (ADA) enzyme in body fluids is a helpful diagnostic tool. Aim: To study the serum Adenosine Deaminase Activity in patients of Pulmonary Tuberculosis and to evaluate the diagnostic significance of ADA activity in serum in these patients. Material and Methods: Present study was carried out in fifty patients of both the sexes with different ages suffering from Pulmonary Tuberculosis attending OPD and ...
This study will evaluate a new method for delivering gene transfer therapy to patients with severe combined immunodeficiency disease (SCID) due to a defective adenosine deaminase (ADA) gene. This gene codes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections.. Some patients with this disease receive enzyme replacement therapy with weekly injections of the drug PEG-ADA (ADAGEN). This drug may increase the number of immune cells and reduce infections, but it is not a cure. Gene transfer therapy, in which a normal ADA gene is inserted into the patient s cells, attempts to correct the underlying cause of disease. This therapy has been tried in a small number of patients with varying degrees of success. In this study, the gene will be inserted into the patient s stem cells (cells produced by the bone marrow that mature ...
Adenosine deaminase (ADA) is a protein produced by cells throughout the body and is associated with the activation of lymphocytes, a type of white blood cell that plays a role in the immune response to infections. The adenosine deaminase test may be used to help determine whether a person has a Mycobacterium tuberculosis infection (TB) of the lining of the lungs (pleurae).
This study addresses three important issues regarding CD/5-FC VDEPT. First, data presented in Figs. 1 ⇓ and 3 ⇓ demonstrate that cell lines derived from both GI and non-GI tumors display similar in vitro sensitivity to both 5-FU and AdCMVCD/5-FC on continuous 5-day drug exposure using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium assay of cellular respiration. Nonparametric analysis of median 5-FU (Fig. 1) ⇓ and AdCMVCD/5-FC (Fig. 3) ⇓ sensitivity (IC50) of 14 tumor cell lines (2 colon, 5 pancreatic, 4 glioma, and 3 prostatic cell lines) revealed no significant differences among the four tumor cell types tested (P = 0.1 and 0.24, respectively). A similar analysis was performed on publicly available 5-FU toxicity data from the National Cancer Institute Developmental Therapeutics Program Disease-oriented Anticancer Drug Screen (28) . The National Cancer Institute screens approximately 10,000 compounds/year using a sulforhodamine B protein ...
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A variety of mutations are accumulated in the genome of HTLV-1 infected T-cells during ATL development. To elucidate the mechanism of ATL development a mouse model of ATL was established by infecting HTLV-1 to humanized NOG mice and the infected mice recapitulate the ATL-like symptoms and die of leukemia within several months of infection. Analysis of gene expressions in the humanized mouse model of ATL demonstrated the induction of APOBEC3B (A3B) gene in the HTLV-1 infected human T-cells. A3B is a member of the APOBEC family of cellular cytidine deaminase and was recently identified as the mutational source in multiple human cancers. We have previously shown that HTLV-1 infected CD25 (-) CD4 T-cells but not CD25 (+) CD4 T-cells in ATL model mouse express a small amount of Tax mRNA even though both cell populations consist of identical infected-cell clones. As the A3B expression in HTLV-1 infected CD25 (+) T-cells was similar to, or rather higher than that in CD25 (-)T-cells, Tax appears not to ...
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Rabbit monoclonal antibody raised against a human ADA peptide using ARM Technology. A synthetic peptide of human ADA is used for rabbit immunization.Customer or Abnova will decide on the preferred peptide sequence. (H00000100-K) - Products - Abnova
Brown, M.R.; Crim, J.W.; Lea, A.O., 1986: FMRFamide- and pancreatic polypeptide-like immunoreactivity of endocrine cells in the midgut of a mosquito
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Adenosine deaminase (ADA) is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues. Present in virtually all mammalian cells, its primary function in humans is the development and maintenance of the immune system. Adenosine deaminase is considered one of the key enzymes of purine metabolism. Adenosine deaminase in humans is involved in the development and maintenance of the immune system. However, Adenosine deaminase association has also been observed with epithelial cell differentiation, neurotransmission, and gestation maintenance. It has also been proposed that Adenosine deaminase, in addition to adenosine breakdown, stimulates release of excitatory amino acids and is necessary to the coupling of A1 adenosine receptors and heterotrimeric G proteins.. ...
AIM: To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 5-fluorocytosine) on human hepatocellular carcinoma. METHODS: CD gene was transduced into human hepatocellular carcinoma cell line
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TY - JOUR. T1 - Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2-deoxycoformycin. AU - Hershfield, M. S.. AU - Kurtzberg, J.. AU - Harden, E.. AU - Moore, J. O.. AU - Whang-Peng, J.. AU - Haynes, B. F.. PY - 1984/3/22. Y1 - 1984/3/22. N2 - Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpectedly, within 7 days of starting treatment, the leukemic phenotype underwent complete conversion from T lymphoblastic to promyelocytic, with kinetics that suggested a precursor-product relationship between the two cell populations. Pretreatment of T lymphoblasts and posttreatment of promyelocytes had the same abnormal karyotype. Upon culture in vitro, the former transformed spontaneously over several weeks into mature myeloid cells. We ...
The human cytidine deaminase Apobec3F (h-A3F) a protein linked to the previously recognized antiviral factor Apobec3G (h-A3G) has antiviral activity against individual immunodeficiency virus type 1 (HIV-1) thats suppressed with the viral protein Vif. E3 ubiquitin ligase. Disturbance with Cul5-E3 ligase function by depletion of Cul5 through RNA disturbance or overexpression of Cul5 mutants obstructed the power of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that didnt recruit Cul5-E3 ligase but was still in a position to connect to h-A3F didnt suppress h-A3F. Oddly enough disturbance with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also elevated the balance of HIV-1 Vif recommending that just like the substrate substances h-A3F and h-A3G the substrate receptor proteins Vif is certainly itself also governed by Cul5-E3 ligase. Our outcomes indicate that Cul5-E3 ligase is apparently a common pathway hijacked by HIV-1 Vif to beat both h-A3F and h-A3G. Developing ...
Synonyms for adenosine deaminase conjugated with polyethylene glycol in Free Thesaurus. Antonyms for adenosine deaminase conjugated with polyethylene glycol. 2 words related to adenosine: biochemistry, nucleoside. What are synonyms for adenosine deaminase conjugated with polyethylene glycol?
OBJECTIVE: Adenosine deaminase (ADA) may be multifunctional, regulating adenosine levels and adenosine receptor (AR) agonism, and potentially modifying AR functionality. Herein we assess effects of ADA (and A(1)AR) deficiency on AR-mediated responses and ischaemic tolerance. METHODS: Normoxic function and responses to 20 or 25min ischaemia and 45min reperfusion were studied in isolated hearts from wild-type mice and from mice deficient in ADA and/or A(1)ARs. RESULTS: Neither ADA or A(1)AR deficiency significantly modified basal contractility, although ADA deficiency reduced resting heart rate (an effect abrogated by A(1)AR deficiency). Bradycardia and vasodilation in response to AR agonism (2-chloroadenosine) were unaltered by ADA deficiency, while A(1)AR deficiency eliminated the heart rate response. Adenosine efflux increased 10- to 20-fold with ADA deficiency (at the expense of inosine). Deletion of ADA improved outcome from 25min ischaemia, reducing ventricular diastolic pressure (by 45%; ...
To confirm the clinical diagnosis of ADA deficiency, it is first necessary to assess the patients immune function.. The workup should start with a complete blood cell (CBC) count with differential to determine absolute lymphocyte count, as well to assess lymphoid subpopulations/markers (i.e., percentages and absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and natural killer (NK) cell markers (CD16 and CD56)). In all ADA SCID patients, T cells, B cells, and NK cells are severely affected (T-B-NK- phenotype).. Lymphopenia with an absolute lymphocyte count of less than 2500 cells/mL in an infant definitely requires further testing. Any infant with severe or opportunistic infection should have the full diagnostic assessment. On average, SCID patients have less than 1500 lymphocytes/mL.. Total serum immunoglobulin (Ig) levels of IgG, IgA, IgM, and IgE should be obtained. All immunoglobulin classes are usually decreased, but not always.. Evaluation of lymphocyte function ...
Strimvelis is the first ex-vivo stem cell gene therapy to treat patients with a very rare disease called ADA-SCID (Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency), a rare disorder caused by the absence of an essential protein called adenosine deaminase (ADA), which is required for the production of lymphocytes. Children born with ADA-SCID do not develop a healthy immune system so cannot fight off everyday infections, which results in severe and life-threatening illness. Without prompt treatment, the disorder often proves fatal within the childs first year of life. ADA-SCID is estimated to occur in approximately 15 patients per year in Europe. The treatment was developed at San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) and developed by GlaxoSmithKline (GSK) through a 2010 collaboration with Fondazione Telethon and Ospedale San Raffaele (OSR). GSK, working with the biotechnology company MolMed S.p.A, developed a manufacturing process that was previously only ...
TY - JOUR. T1 - Gene transfer and antisense nucleic acid techniques. AU - Miller, N.. AU - Vile, R. G.. PY - 1994. Y1 - 1994. N2 - Attempts to suppress a harmful genetic trait by antisense means, or to restore a normal phenotype by gene transfer, attract much publicity. This is especially the case where clinical trials incorporating such methodologies have been initiated, such as antisense oligonucleotide therapies for some types of leukaemia, antisense gene-transfer therapy for a form of lung cancer, and gene-transfer therapies for adenosine deaminase deficiency, severe combined immunodeficiency disease, and various forms of cancer including brain tumours and melanoma. However, translation of laboratory success into treatment or control of disease is unlikely to be straightforward. Here, Nick Miller and Richard Vile summarize the rationale, problems and potential of such techniques as applied to parasitic disease.. AB - Attempts to suppress a harmful genetic trait by antisense means, or to ...
Dipeptidyl peptidase II (DPPII) from bovine kidney cortex and lung was purified to the electrophoretically homogeneous state. The molecular and catalytic characteristics of the enzyme were determined. It was revealed that DPPII preparations possess adenosine deaminase (ADA) activity at all purificat …
Xeomin® is the third botulinum toxin type A licensed in the UK as a prescription only medicine. It is an innovative Botulinum type A formulation, in which the complexing proteins have been removed. You will require a face-to-face consultation with a prescriber to determine your suitability for treatment.
ID B3CKG9_SIV Unreviewed; 208 AA. AC B3CKG9; DT 22-JUL-2008, integrated into UniProtKB/TrEMBL. DT 22-JUL-2008, sequence version 1. DT 10-FEB-2021, entry version 42. DE RecName: Full=Virion infectivity factor {ECO:0000256,RuleBase:RU003341}; GN Name=vif {ECO:0000313,EMBL:CAP72505.1}; OS SIV-wrc Pbt-05GM-X02. OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus. OX NCBI_TaxID=498715 {ECO:0000313,EMBL:CAP72505.1, ECO:0000313,Proteomes:UP000257744}; RN [1] {ECO:0000313,EMBL:CAP72505.1, ECO:0000313,Proteomes:UP000257744} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=wrcPbt-05GM-X02 {ECO:0000313,Proteomes:UP000257744}; RX PubMed=18442839; DOI=10.1016/j.virol.2008.01.049; RA Locatelli S., Lafay B., Liegeois F., Ting N., Delaporte E., Peeters M.; RT Full molecular characterization of a simian immunodeficiency virus, RT SIVwrcpbt from Temmincks red colobus (Piliocolobus badius temminckii) from RT Abuko Nature ...
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BioAssay record AID 449980 submitted by ChEMBL: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in HeLa cells at 1 uM by microplate beta scintillation counting.
Rabbit polyclonal antibody raised against partial recombinant human APOBEC3G. Recombinant protein corresponding to human APOBEC3G. (PAB30317) - Products - Abnova
偵測人類胸膜液(Pleural fluid) 腺核?脫胺基?(Adenosine deaminase, ADA)所含的量,以幫助結核性肋膜炎的診斷。結核菌感染時,腦脊髓液(CSF)檢體中之ADA濃度會較其他細菌性、病毒性感染或惡性腫瘤疾病為高。 ...
This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions ...
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Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
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HIV lacking Vif is susceptible to human APOBEC3 (A3)-mediated restriction, rendering the virus non-infectious. The archetypal family member, A3G, has a well-def...
Project details This project will use novel genetic approaches to study the role of hypermutation in the development of bladder cancer. Cytidine deaminases from the APOBEC-family make a major contribution to the mutational landscape of cancers from the bladder, the breast and the lung.
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Human APOBEC3F Full-length ORF (NP_001006667.1, 1 a.a. - 101 a.a.) Recombinant Protein with GST-tag at N-terminal, Abnova; For use in AP, Array, ELISA, WB-Re Shop Abnova™ Human
adenosine deaminase ENTREZID: 100 | Type: Protein Coding | Map: 20q13.12 OMIM: 300335 Summary Entrez This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway.
Summary of ANO7 (IPCA-5, NGEP, PCANAP5, PCANAP5L, TMEM16G) expression in human tissue. Cytoplasmic expression in prostate and stomach glands.
agan n sista sekalian.. ane mau tanya ni sebelumnya sebenarnya ada ga si kaskus award di kaskus? klo ada kapan n bagaimana biasanya?(maklum an bukan anggota kaskus yg aktif bgt nongkrongn kaskus...) :ngakak klo dipikiran ane si coba di setiap bulannya ada kaskuser of the month , kan seru tuh..hee atau misalkan bisa di buat setiap 6 bulan sekali ada penghargaan untuk kaskuser.. mungkin ada kategori
cv-8F-BFS: Well, since nobody wants to comment on this one, I will. I think this page is fairly easy to understand, it could have used some more PIZAZZ!!! but over all good work ...
It is created from guanine by guanine deaminase. It is created from hypoxanthine by xanthine oxidoreductase. It is also created ... from xanthosine by purine nucleoside phosphorylase. Xanthine is subsequently converted to uric acid by the action of the ...
Carter CW (1998). "Nucleoside deaminases for cytidine and adenosine: comparisons with deaminases acting on RNA". In Grosjean H ... The adenosine deaminase of E. coli cannot deaminate a nucleoside in the RNA; the enzyme's reaction pocket is too small for the ... The editing involves cytidine deaminase that deaminates a cytidine base into a uridine base. An example of C-to-U editing is ... More often than not, modifications cause an increase in mass for a given nucleoside. This gives a characteristic readout for ...
... deaminase deficiency is a known cause of immunodeficiency. The adenosine analog NITD008 has been reported to directly ... Adenosine is one of four nucleoside building blocks to DNA and RNA, which are essential for all life. Its derivatives include ... When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in red blood cells and the ... Dipyridamole, an inhibitor of adenosine nucleoside transporter, allows adenosine to accumulate in the blood stream. This causes ...
If the nucleoside is adenosine, it is acted upon by adenosine deaminases to convert it into inosine. This metabolite, in turn, ... The nucleosides cytidine and deoxycytidine can be salvaged along the uracil pathway by cytidine deaminase, which converts them ... The nucleosides are taken up in the cell by transporters and are funneled through the salvage pathway. ... Nucleotide salvage pathways are used to recover bases and nucleosides that are formed during degradation of RNA and DNA. This ...
The other purine nucleoside, guanosine, is cleaved to form guanine. Guanine is then deaminated via guanine deaminase to form ... The conversion of a nucleoside-diphosphate (NDP) to a nucleoside-triphosphate (NTP) is catalyzed by nucleoside diphosphate ... The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and nucleosidase ... Purine and pyrimidine nucleosides can either be degraded to waste products and excreted or can be salvaged as nucleotide ...
... decreased purine nucleoside phosphorylase and adenosine deaminase activity". Blut. 39 (5): 309-15. doi:10.1007/BF01014193. PMID ... It has the unique ability to metabolize cytokinins-a plant hormone that can exist as a base, nucleotide, or nucleoside-into ...
... is a nucleoside analog of cytidine. It is a transition state analog inhibitor of cytidine deaminase by binding to ...
It mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, interfering with the cell's ability to ...
The nucleoside form of AICAR, acadesine, is an analog of adenosine that enters cardiac cells to inhibit adenosine kinase and ... AICAR is able to enter the de novo synthesis pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase ... adenosine deaminase. It enhances the rate of nucleotide re-synthesis increasing adenosine generation from adenosine ...
... is the first of a series of cancer drugs that altered the sugar component of nucleosides. Other cancer drugs modify ... Drake JC, Hande KR, Fuller RW, Chabner BA (Mar 1980). "Cytidine and deoxycytidylate deaminase inhibition by uridine analogs". ... Cytarabine is in the antimetabolite and nucleoside analog families of medication. It works by blocking the function of DNA ... Cytarabine is rapidly deaminated by cytidine deaminase in the serum into the inactive uracil derivative. Cytarabine-5´- ...
ApoBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.[1]It is a member of the cytidine deaminase family. ApoBEC- ... A region called the spacer element is found 2-8 nucleotides between the edited nucleoside and this mooring sequence. There is ... Editing occurs post transcriptionally as the nascent polynucleotides do not contain edited nucleosides. C to U editing of ApoB ... "Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate ...
It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine. The ... Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nucleoside monophosphate). Widely used as a flavor ...
peripheral: Purine nucleoside phosphorylase deficiency *Hyper IgM syndrome (1). Severe combined. (B+T). *x-linked: X-SCID. ...
peripheral: Purine nucleoside phosphorylase deficiency *Hyper IgM syndrome (1). Severe combined. (B+T). *x-linked: X-SCID. ...
... nucleoside deaminases MeSH D08.811.277.151.486.075 - adenosine deaminase MeSH D08.811.277.151.486.250 - cytidine deaminase MeSH ... nucleotide deaminases MeSH D08.811.277.151.653.060 - amp deaminase MeSH D08.811.277.151.653.200 - dcmp deaminase MeSH D08.811. ... nucleoside-diphosphate kinase MeSH D08.811.913.696.650.575 - nucleoside-phosphate kinase MeSH D08.811.913.696.900 - ... purine-nucleoside phosphorylase MeSH D08.811.913.400.725.900 - thymidine phosphorylase MeSH D08.811.913.400.725.950 - uridine ...
... reveals distinct domains that mediate cytosine nucleoside deaminase, RNA binding, and RNA editing activity". J. Biol. Chem. 270 ... This gene encodes a member of the APOBEC protein family and the cytidine deaminase enzyme family. The encoded protein forms a ... Gonzalez MC, Suspène R, Henry M, Guétard D, Wain-Hobson S, Vartanian JP (2009). "Human APOBEC1 cytidine deaminase edits HBV DNA ... Smith H (12 September 2008). "The APOBEC1 Paradigm for Mammalian Cytidine Deaminases That Edit DNA and RNA" (PDF). In Henri ...
The enzyme nucleoside monophosphate kinase converts UMP and ATP to uridine diphosphate (UDP) and ADP. In the presence of excess ... DCMP deaminase Uridine monophosphate Berg, J. M.; Tymoczko, J. L.; Stryer, L. (2002). Biochemistry (5th ed.). New York: W H ...
Carson had studied adenosine deaminase deficiency and recognized that because the lack of adenosine deaminase led to the ... Chemically, it mimics the nucleoside adenosine. However, unlike adenosine it is relatively resistant to breakdown by the enzyme ... which renders it partially resistant to breakdown by adenosine deaminase (ADA). In cells it is phosphorylated into its toxic ... A Potent Chemotherapeutic and Immunosuppressive Nucleoside". Leukemia & Lymphoma. 5 (1): 1-8. doi:10.3109/10428199109068099. ...
AMP deaminase creates inosinic acid, then a nucleotidase creates inosine Purine nucleoside phosphorylase acts upon inosine to ... Some of the diseases are: Severe immunodeficiency by loss of adenosine deaminase. Hyperuricemia and Lesch-Nyhan syndrome by the ... A nuclease frees the nucleotide A nucleotidase creates guanosine Purine nucleoside phosphorylase converts guanosine to guanine ... strictly regioselective prebiotic purine nucleoside formation pathway. Science. 2016 May 13;352(6287):833-6. doi: 10.1126/ ...
It is a nucleoside analog and therefore has to be phosphorylated to be active. This is a three-step process in which vidarabine ... The use of an inhibitor of adenosine deaminase to increase the half-life of vidarabine has also been tried, and drugs such as ... Other nucleoside analogs need to be triphosphorlated to give any antiviral effect, but ara-ADP inhibits the enzyme ... It was the first nucleoside analog antiviral to be given systemically and was the first agent to be licensed for the treatment ...
Note: adenosine is first metabolized to inosine via the enzyme adenosine deaminase. Nucleoside phosphorylase is an enzyme which ... Purine nucleoside phosphorylase (PNP) also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by ... Purine nucleoside phosphorylase deficiency Canduri F, dos Santos DM, Silva RG, Mendes MA, Basso LA, Palma MS, de Azevedo WF, ... Borgers M, Verhaegen H, De Brabander M, De Cree J, De Cock W, Thoné F, Geuens G (Nov 1978). "Purine nucleoside phosphorylase in ...
2007). "Adenosine deaminase 1 and concentrative nucleoside transporters 2 and 3 regulate adenosine on the apical surface of ... Concentrative nucleoside transporters Nucleoside transporters Solute carrier family GRCh38: Ensembl release 89: ENSG00000137860 ... "Molecular determinants of specificity for synthetic nucleoside analogs in the concentrative nucleoside transporter, CNT2". J. ... Concentrative nucleoside transporter 2 (CNT2) is a protein that in humans is encoded by the SLC28A2 gene. ...
In contrast to adenosine deaminase deficiency (another deficiency of purine metabolism), there is minimal disruption to B cells ... Purine nucleoside phosphorylase deficiency, is a rare autosomal recessive metabolic disorder which results in immunodeficiency ... The disorder is caused by a mutation of the purine nucleoside phosphorylase (PNP) gene, located at chromosome 14q13.1. This ... Toro A, Grunebaum E (Oct 2006). "TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency ...
T-/B- SCID (both T and B cells absent): RAG 1/2 deficiency, DCLRE1C deficiency, adenosine deaminase (ADA) deficiency, reticular ... Omenn syndrome DNA ligase type IV deficiency Cernunnos deficiency CD40 ligand deficiency CD40 deficiency Purine nucleoside ...
2003). "Human cytidine deaminase: understanding the catalytic mechanism". Nucleosides, Nucleotides & Nucleic Acids. 22 (5-8): ... Taysi S, Polat MF, Sari RA, Bakan E (May 2002). "Serum adenosine deaminase and cytidine deaminase activities in patients with ... "Intersubunit interactions in human cytidine deaminase". Nucleosides, Nucleotides & Nucleic Acids. 22 (5-8): 1535-8. doi:10.1081 ... Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene. This gene encodes an enzyme involved in pyrimidine ...
A nucleoside analog, blasticidin S resembles the nucleoside cytidine. The chemical structure consists of a cytosine molecule, ... Both deaminases work by modifying blasticidin S directly, replacing the amine on the cytosine ring with a hydroxyl group, ... Blasticidin S is a nucleoside analogue antibiotic, resembling the nucleoside cytidine. Blasticidin works against human cells, ... Resistance to blasticidin S can be conferred by either of two deaminases: BSD, originally isolated from Aspergillus terreus or ...
Cytidine deaminase questionable: not present in very high levels at all CPNE1 ENSA (gene) FTH1 Heavy chain of Ferritin GDI2 rab ... Nucleoside diphosphate kinase NONO P4HB PRDX1 peroxiredoxin (reduces peroxides) PTMA Prothymosin RPA2 Binds DNA during ...
The "open" and "closed" states refer to the nucleoside binding site on dCK. dCK is a key enzyme in the nucleoside salvage ... which is gemcitabine's active form which inhibits both deoxycytidylate deaminase and DNA polymerase. Although gemcitabine has ... Nucleoside-diphosphate kinase or nucleoside kinase A adds the third phosphoryl group to form dFdCTP (gemcitabine triphosphate ... phosphorylates several deoxyribonucleosides and their nucleoside analogues (a nucleoside with a sugar and a different nucleic ...
Bass BL (2002). "RNA editing by adenosine deaminases that act on RNA". Annu. Rev. Biochem. 71: 817-846. doi:10.1146/annurev. ... CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside ...
It is deaminated intracellularly by adenosine deaminase to dioxolane guanine (DXG). DXG-triphosphate, the active form of the ... Addition of the second phosphate group to nucleoside monophosphate analogues is completed by the nucleoside monophosphate ... Many nucleoside analogues were prepared and examined but only one had significant activity and satisfied the requirements for ... The first nucleoside reverse-transcriptase inhibitor with in vitro anti-HIV activity was zidovudine. Since zidovudine was ...
Ito ay nalilikha mula sa guanine sa pamamagitan ng guanine deaminase.. *Ito ay nalilikha mula sa hypoxanthine sa pamamagitan ng ... Ito ay nalilikha mula sa xanthosine ng purine nucleoside phosphorylase(PNP).[2] ...
Anti-metabolites resemble either nucleobases or nucleosides (a nucleotide without the phosphate group), but have altered ... Adenosine deaminase inhibitor (Pentostatin). *Halogenated/ribonucleotide reductase inhibitors (Cladribine. *Clofarabine. * ...
Adenosine deaminase deficiency. *Purine nucleoside phosphorylase deficiency. *Xanthinuria. *Gout. *Mitochondrial ...
2001). "Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes ... 2003). "Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ... "Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists". Current Pharmaceutical Design 8 (26): 2285-98. ...
... and adenosine deaminases in Eukarya), which increase the decoding capacity of a given tRNA.[31] As an example, tRNAAla encodes ... "Modified nucleosides in transfer RNA". Accounts of Chemical Research. 10 (11): 403-410. doi:10.1021/ar50119a004. Retrieved 23 ...
Adenosine deaminase. *Purine nucleoside phosphorylase. *Guanine deaminase. *Xanthine oxidase. *Urate oxidase. Pyrimidine ...
Guanine deaminase. *cytosine. सन्दर्भ[संपादित करें]. *↑ Levy, Matthew; Stanley L. Miller, John Oró (August 1999). "Production ... Nucleobases, nucleosides, and nucleotides. Nucleobases. Purine (Adenine, Guanine, Purine analogue) · Pyrimidine (Uracil, ...
It is also created from xanthosine by purine nucleoside phosphorylase (PNP).[3] ... It is created from guanine by guanine deaminase.. *It is created from hypoxanthine by xanthine oxidoreductase. ...
Nucleoside and. nucleotide (NRTI). *Nucleoside analogues/NRTIs: Abacavir (ABC)°#. *Didanosine (ddI). *Emtricitabine (FTC)° ... Adenosine deaminase inhibitor (Pentostatin). *Halogenated/ribonucleotide reductase inhibitors (Cladribine. *Clofarabine. * ...
McCloskey JA, Nishimura S (November 1977). "Modified nucleosides in transfer RNA". Accounts of Chemical Research. 10 (11): 403- ... and adenosine deaminases in Eukarya), which increase the decoding capacity of a given tRNA.[32] As an example, tRNAAla encodes ...
Non-nucleoside reverse-transcriptase inhibitors. *NS5A inhibitors. *Nucleoside and nucleotide reverse-transcriptase inhibitors ... Adenosine deaminase inhibitor (Pentostatin). *Halogenated/ribonucleotide reductase inhibitors (Cladribine. *Clofarabine. * ...
... it is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-. AMP ... AMP can be converted into IMP by the enzyme myoadenylate deaminase, freeing an ammonia group. In a catabolic pathway, adenosine ... nucleoside monophosphates, including adenosine monophosphate, are formed. AMP can be regenerated to ATP as follows: AMP + ATP ...
APC Adenosine deaminase deficiency, partial; 102700; ADA Adenosine triphosphate, elevated, of erythrocytes; 102900; PKLR ... MAPBPIP Immunodeficiency due to purine nucleoside phosphorylase deficiency; 613179; PNP Immunodeficiency with hyper IgM, type 4 ...
Nucleoside analogues such as 2-aminopurine and 5-bromouracil can insert in place of A and T respectively. Ionizing radiation ... Two of the most prevalent deaminase reactions occur through the Apolipoprotein B mRNA editing enzyme (APOBEC) and the adenosine ... RNA editing-dependent amino acid substitutions can produce missense mRNA's of which occur through hydrolytic deaminase ... deaminase acting on RNA enzyme (ADAR) which are responsible for the conversion of cytidine to uridine (C-to-U), and the ...
May 2009). "Alternative induction of meiotic recombination from single-base lesions of DNA deaminases". Genetics. 182 (1): 41- ... "A mammalian-like DNA damage response of fission yeast to nucleoside analogs". Genetics. 193 (1): 143-57. doi:10.1534/genetics. ...
In addition, active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC family of cytosine deaminases could ... Hotchkiss RD (1948). "The quantitative separation of purines, pyrimidines and nucleosides by paper chromatography". J Biol Chem ... 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine. In 5-methylcytosine, a methyl group is attached to the 5th ...
... adenosine deaminase acting on RNA catalytic 2 domain) and MCP (MS2 capsid protein). The binding of the ADAR2 enzyme to the RNA ... adding a temporal dimension to RNA sequencing through nucleoside recoding". Nature Methods. 15 (3): 221-225. doi:10.1038/nmeth. ... human adenosine deaminase acting on RNA 2 catalytic domain). The ADAR2cd enzyme is targeted to specifically bind to MS2 sites, ...
... to the corresponding nucleoside (e.g. adenosine) which can readily enter most cells. Consequently, the enzyme plays a key role ... association with adenosine deaminase deficiency and nonassociation with deoxyadenosine toxicity". Clinical Immunology and ... with the nucleoside acting as a leaving group. Studies of mammalian 5'nucleotidases have shown that there exist at least four ... a nucleoside + phosphate ribose 5-phosphate + H2O ⇌ ribose + phosphate The 5'nucleotidase catalyzed reaction of an AMP ...
Patients with adenosine deaminase deficiency (ADA) tend to have elevated intracellular dATP concentrations because adenosine ... It is classified as a purine nucleoside triphosphate, with its chemical structure consisting of a deoxyribose sugar molecule ... Research has found that dATP may be a potential toxic metabolite in adenosine deaminase deficiency. Patients in the study who ... Cowan MJ, Wara DW, Ammann AJ (October 1985). "Deoxycytidine therapy in two patients with adenosine deaminase deficiency and ...
Active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC family of cytosine deaminases could have both ... The nucleoside of cytosine is cytidine. In Watson-Crick base pairing, it forms three hydrogen bonds with guanine. Cytosine was ...
A modified form of bovine adenosine deaminase used to treat adenosine deaminase deficiency, a condition which leads to the ...
Heat-induced formation of alpha,beta-unsaturated nucleoside dialdehydes and their activity with adenosine deaminase.. Grant AJ ... Heating of nucleoside dialdehydes at any time is not recommended. The exact composition of nucleoside dialdehydes used in ... Application of heat to aqueous solutions of nucleoside dialdehydes (periodate-oxidized nucleosides) affords the corresponding ... The reaction was first discovered during studies with adenosine deaminase and was initially investigated enzymatically until ...
We studied an Arab family in which two infants died of severe combined immunodeficiency caused by adenosine deaminase (ADA) ... One infant had purine nucleoside phosphorylase (PNP) activity in the leucocytes only half that of normal. Four other infant ...
Localization of adenosine deaminase [ADA] and purine nucleoside phosphorylase [PNP] in human hepatic and renal tissues - ... lymphatic tissue nucleoside adenosine man endothelial cell purine nucleoside phosphorylase hepatic tissue kidney liver renal ...
Muscle nucleotide/nucleoside and base analysis. Portions (5-10 mg wet weight) of muscle biopsies were homogenized in ice cold ... Hisatome, I., Morisake, T., Kamma, H., Sugama, T., Morisaki, H., Ohtahara, A. & Holmes, E. W. (1998). Control of AMP deaminase ... Shumate J. B., Katnik, R., Ruiz, M., Kaiser, K., Frieden, C., Brooke, M. H. & Carroll, J. E. (1979). Myoadenylate deaminase ... Sinkeler S. P., Binkhorst, R. A., Joosten, E. M., Wevers, R. A., Coerwinkei, M. M. & Oei, T. L. (1987). AMP deaminase ...
Nucleoside Deaminases / genetics * Nucleoside Deaminases / metabolism * Prodrugs / therapeutic use Substances * Prodrugs * ... coli cytosine deaminase (CD) gene and show that systemically injected spores of these bacteria express CD only in the tumor. ...
Adenosine Deaminase from bovine spleen Type X, buffered aqueous glycerol solution, ≥130 units/mg protein; CAS Number: 9026-93-1 ... nucleoside phosphorylase ≤0.1% storage temp. 2-8°C Gene Information cow ... ADA(280712) ... Adenosine deaminase is useful in various molecular biology assays, such as glycerol release assays . Adenosine deaminase is a ... Adenosine Deaminase from bovine spleen Type X, buffered aqueous glycerol solution, ≥130 units/mg protein Synonym: Adenosine ...
... adenosine deaminase; purine nucleoside phosphorylase; transporter 1 and 2, ATP-binding cassette (TAP1, TAP2); 4 components of ... Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29. 360(5):447-58. [Medline]. ... Hyper-IgM syndromes (including deficiencies of CD40 ligand (CD154), activation-induced cytidine deaminase [AID], and uracil- ... nucleoside-glycosylase [UNG]): This is a heterogeneous group of disorders in which normal or elevated IgM levels are found ...
Adenosine deaminase deficiency. *Purine nucleoside phosphorylase deficiency. *For patients who have had a prior HCT, any ...
Adenosine deaminase deficiency. *Purine nucleoside phosphorylase deficiency. *X-linked SCID. *Common variable immune deficiency ...
Adenosine deaminase deficiency. *Purine nucleoside phosphorylase deficiency. *X-linked SCID. *Common variable immune deficiency ...
To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 5- ... 0/Antineoplastic Agents; 0/Prodrugs; 2022-85-7/Flucytosine; EC 3.5.4.-/Nucleoside Deaminases; EC 3.5.4.1/Cytosine Deaminase ... Nucleoside Deaminases / genetics*, therapeutic use. Prodrugs / therapeutic use*. Transduction, Genetic. Tumor Cells, Cultured. ... Cytosine Deaminase. Female. Flucytosine / therapeutic use*. Gene Therapy*. Genes, Tumor Suppressor. Humans. Liver Neoplasms / ...
Effects of murine viral leukemia on spleen nucleoside deaminase: purification and properties of the enzyme from leukemic spleen ... Malathi, V.G.; Silber, R., 1971: Effects of murine viral leukemia on spleen nucleoside deaminase: purification and properties ... Effects of murine viral leukemia on spleen nucleoside deaminase: purification and properties of the enzyme from leukemic spleen ...
Keywords: adenosine receptor; adenosine deaminase; purine nucleoside signaling; cell membrane; gastric mucosa parietal cell ... The A2B adenosine receptor colocalizes with adenosine deaminase in resting parietal cells from gastric mucosa by R. M. Arin; A ... Adenosine deaminase (ADA) can degrade adenosine and bind extracellularly to adenosine receptors. Adenosine modulates chloride ...
Adenosine Deaminase Activity Assay Kit (Colorimetric): Simple & convenient assay to measure ada activity in a variety of ... Purine Nucleoside Phosphorylase Activity Assay Kit (Fluorometric). $625.00 Xanthine/Hypoxanthine Colorimetric/Fluorometric ... The kit measures total Activity of Adenosine Deaminase with limit of quantification 1 mU recombinant Adenosine Deaminase.. ... The kit measures total Activity of Adenosine Deaminase with limit of quantification of 1 mU recombinant Adenosine Deaminase. ...
Rabbit Polyclonal Anti-Adenosine Deaminase/ADA Antibody. Validated: WB, ELISA, IP. Tested Reactivity: Human, Mouse, Bovine. 100 ... Blogs on Adenosine Deaminase/ADA. There are no specific blogs for Adenosine Deaminase/ADA, but you can read our latest blog ... PTMs for Adenosine Deaminase/ADA Antibody (NBP1-77775). Learn more about PTMs related to Adenosine Deaminase/ADA Antibody (NBP1 ... Publications for Adenosine Deaminase/ADA Antibody (NBP1-77775) (0). There are no publications for Adenosine Deaminase/ADA ...
Cristalli et al., Diazepinone nucleosides as inhibitors of cytidine deaminase, Nucleosides Nucleotides 15:1567-80 (1996). ... Liu P.S. et al., "Cyclic Urea Nucleosides. Cytidine Deaminase Activity as a Function of Aglycon Ring Size", Journal of ... Kim et al., "Synthesis of Pyrimidin-2-one Nucleosides as Acid-Stable inhibitors of Cytidine Deaminase." J. Med. Chem. 29:1374- ... Marquez V. E. et al., "Synthesis of 1,3-Diazepin-2-one Nucleosides as Transition-State Inhibitors of Cytidine Deaminase", ...
Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past ... with hydrolysis of nucleoside monophosphates [26]. Together, ecto-5′-nucleotidase and adenosine deaminase (ADA; EC 3.5.4.4), ... Hydrolysis of the nucleoside monophosphate to the nucleoside is catalyzed by ecto-5′-nucleotidase. NTPDases, NPPs and alkaline ... They have to be transformed into the corresponding nucleosides that enter cells via specific transporters to rebuild nucleoside ...
... from calf intestine and adenylate deaminase (AMPDA) from Aspergillus species has been evaluated and compared with that of the ... Nucleosides Nucleotides Nucleic Acids. 2008 Jan;27(1):31-6. doi: 10.1080/15257770701571776. ... Activity of adenosine deaminase and adenylate deaminase on adenosine and 2, 3()-isopropylidene adenosine: role of the ... The deamination rate of 2,3-isopropylidene adenosine catalyzed by adenosine deaminase (ADA) from calf intestine and adenylate ...
nucleoside 5-triphosphate. PBGD. porphobilinogen deaminase. PCBP. poly (rC) binding protein. PHD. prolyl hydroxylase ...
2003). "Human cytidine deaminase: understanding the catalytic mechanism". Nucleosides, Nucleotides & Nucleic Acids. 22 (5-8): ... Taysi S, Polat MF, Sari RA, Bakan E (May 2002). "Serum adenosine deaminase and cytidine deaminase activities in patients with ... "Intersubunit interactions in human cytidine deaminase". Nucleosides, Nucleotides & Nucleic Acids. 22 (5-8): 1535-8. doi:10.1081 ... Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene. This gene encodes an enzyme involved in pyrimidine ...
Cyclic urea nucleosides. Cytidine deaminase activity as a function of aglycon ring size. ... Synthesis of 1,3-diazepin-2-one nucleosides as transition-state inhibitors of cytidine deaminase. ... Lipophilic, adenosine deaminase-activated prodrugs.. Barchi JJ Jr, Marquez VE, Driscoll JS, Ford H Jr, Mitsuya H, Shirasaka T, ... A carbocyclic nucleoside with antitumor and antiviral properties.. Marquez VE, Lim MI, Treanor SP, Plowman J, Priest MA, ...
Dextran-Bound Purine Nucleosides-Substrates and Inhibitors of Adenosine Deaminase. Affinity Binding Used as a Tool to ...
Single Agent Chemotherapy: Nucleoside Analogues. Pentostatin is a nucleoside analog that inhibits adenosine deaminase.32 Used ... Fludarabine is a nucleoside analogue that resists deamination by adenosine deaminase and is phosphorylated to F-ara-adenosine ... Gemzar is another nucleoside analogue, a pyrimidine with a lower toxicity profile that some of the agents mentioned above.34 ... and a small molecule inhibitor of purine nucleoside phosphorylase (Bcx 1777). Other agents as well as new experimental ...
Abbreviations: ADA, adenosine deaminase; AMPDA, myoadenylate deaminase; BAPAT, β‐alanine-pyruvate aminotransferase; BAKAT, β‐ ... The pyrimidine nucleosides are then taken up by tissues expressing the relevant kinases. In liver, uridine and thymidine are ... 2001) A novel bipartite splicing enhancer promotes the inclusion of a mini‐exon in the AMP deaminase 1 gene. Journal of ... The purine nucleotides IMP and GMP are degraded via the corresponding nucleosides to the constituent bases hypoxanthine and ...
Cytidine Deaminase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... nucleoside binding. IDA. 15689149. GO:0003824. catalytic activity. IEA. --. GO:0004126. cytidine deaminase activity. EXP,IDA. ... cytidine deaminase,pyrimidine catabolic pathway *CDA. UniProtKB/Swiss-Prot CatalyticActivity: Cytidine + H(2)O = uridine + NH(3 ... Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples. (PMID: 18600531) Giovannetti E … ...
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process. nucleobase, nucleoside and nucleotide metabolic process ... Showing Protein Cytidine deaminase (HMDBP05584). IdentificationBiological propertiesGene propertiesProtein propertiesExternal ... Kuhn K, Bertling WM, Emmrich F: Cloning of a functional cDNA for human cytidine deaminase (CDD) and its use as a marker of ... Chung SJ, Fromme JC, Verdine GL: Structure of human cytidine deaminase bound to a potent inhibitor. J Med Chem. 2005 Feb 10;48( ...
Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases. J Biol Chem. 1995 Jun 2;270(22):13042-56 ... J:281668 Caval V, et al., Mouse APOBEC1 cytidine deaminase can induce somatic mutations in chromosomal DNA. BMC Genomics. 2019 ...
UAdenosine deaminase. Not Available. Humans. Absorption. Not Available. Volume of distribution. Not Available. Protein binding ... Nucleosides, nucleotides, and analogues. Class. Purine nucleosides. Sub Class. Not Available. Direct Parent. Purine nucleosides ... Purine nucleoside / Glycosyl compound / N-glycosyl compound / Pentose monosaccharide / Purinone / Imidazopyrimidine / Purine / ... This compound belongs to the class of organic compounds known as purine nucleosides. These are compounds comprising a purine ...
6. Human adenosine deaminase (990). 7. Human purine nucleoside phosphorylase (990). 8. Human hypoxanthine granine phosphoribosl ...
  • We studied an Arab family in which two infants died of severe combined immunodeficiency caused by adenosine deaminase (ADA) deficiency. (bmj.com)
  • Chung SJ, Fromme JC, Verdine GL: Structure of human cytidine deaminase bound to a potent inhibitor. (hmdb.ca)
  • EPI01 is a novel, orally available, disease-modifying therapy that consists of a fixed-dose formulation of a DNA methyl-transferase enzyme 1 and cytidine deaminase inhibitor, decitabine and tetrahydrouridine. (thefreedictionary.com)
  • To assess the effect of MTX on the vasodilator effects of adenosine and the nucleoside uptake inhibitor, dipyridamole, in humans in vivo as a marker for changes in adenosine kinetics. (bmj.com)
  • The novel non-nucleoside ADA inhibitor FR242685 was daily injected into the right ankle of each rat. (nii.ac.jp)
  • However, coadministration with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the AUC of the parent compound more than 4-fold. (clinicaltrials.gov)
  • The sensitivity of clinically derived resistant HIV-1 strains to nucleotide RT inhibitors could be restored, however, in several laboratories by pharmacological depletion of the appropriate endogenous deoxynucleotide triphosphate (dNTP), and such a manipulation (induction of dCTP pool imbalance during reverse transcription in the presence of a non-nucleoside RT inhibitor) altered the mutation spectrum of the HIV-1 genome, resulting in a lower level of HIV resistance to certain drugs. (ingentaconnect.com)
  • A modified form of bovine adenosine deaminase used to treat adenosine deaminase deficiency, a condition which leads to the formation of adenosine metabolites which are cytotoxic to lymphocytes. (drugbank.ca)
  • 1 Myoadenylate deaminase (AMPD) deficiency is present in 1-2 % of the population. (wiley.com)
  • It is ubiquitous in mammalian tissue, and deficiency in adenosine deaminase has been associated with severe combined immunodeficiency disease. (sigmaaldrich.com)
  • Mutations which result in nucleoside phosphorylase deficiency result in defective T-cell (cell-mediated) immunity but can also affect B-cell immunity and antibody responses. (genecards.org)
  • Diseases associated with PNP include Immunodeficiency Due To Purine Nucleoside Phosphorylase Deficiency and Adenosine Deaminase Deficiency . (genecards.org)
  • Adenosine deaminase deficiency (ADA) is an inherited condition that affects the immune system and typically leads to severe combined immunodeficiency (SCID) . (nih.gov)
  • In most cases, signs and symptoms of adenosine deaminase deficiency (ADA) develop before 6 months of age. (nih.gov)
  • Adenosine deaminase deficiency is caused by changes ( mutations ) in the ADA gene . (nih.gov)
  • Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). (bloodjournal.org)
  • Adenosine deaminase (ADA) deficiency is a rare inherited disorder of purine metabolism characterized by the accumulation of metabolic substrates that lead to abnormalities of immune system development and function and a variety of systemic defects. (bloodjournal.org)
  • Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. (thefreedictionary.com)
  • AIP is a dominantly inherited condition resulting from the deficiency of PBG deaminase , which leads to markedly elevated urinary ALA and PBG during an acute attack. (thefreedictionary.com)
  • The serendipitous discovery of adenosine deaminase (ADA) deficiency in two patients with cellular immunodeficiency in 1972 by Dr. Eloise Giblett and colleagues ( 1 ) ushered in a new era in the investigation of the molecular mechanisms underlying primary immunodeficiency disorders. (jimmunol.org)
  • Purine nucleoside phosphorylase deficiency is a disorder of the immune system called an immunodeficiency. (medlineplus.gov)
  • The shortage of immune system cells in people with purine nucleoside phosphorylase deficiency results in repeated and persistent infections typically beginning in infancy or early childhood. (medlineplus.gov)
  • The infections can be very serious or life-threatening, and without successful treatment to restore immune function, children with purine nucleoside phosphorylase deficiency usually do not survive past childhood. (medlineplus.gov)
  • Infants with purine nucleoside phosphorylase deficiency typically grow more slowly than healthy babies. (medlineplus.gov)
  • People with purine nucleoside phosphorylase deficiency are also at increased risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs. (medlineplus.gov)
  • Purine nucleoside phosphorylase deficiency is caused by mutations in the PNP gene. (medlineplus.gov)
  • The shortage of T cells and sometimes B cells results in the immune problems characteristic of purine nucleoside phosphorylase deficiency. (medlineplus.gov)
  • Damage to brain cells caused by buildup of dGTP is thought to underlie the neurological problems that occur in some people with purine nucleoside phosphorylase deficiency. (medlineplus.gov)
  • See Omenn Syndrome and Purine Nucleoside Phosphorylase Deficiency for a discussion of other forms of SCID. (medscape.com)
  • Deficiency of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) elevates intracellular levels of deoxyguanosine and deoxyadenosine, respectively. (medscape.com)
  • 2. Two sisters with chronic respiratory disease and recurrent infections were identified as the first cases of adult onset immunodeficiency due to adenosine deaminase deficiency. (portlandpress.com)
  • affected child with partial adenosine deaminase deficiency is GM08832. (coriell.org)
  • Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme which plays a key role in the purine salvage pathway, and PNP deficiency in humans leads to an impairment of T-cell function, usually with no apparent effect on B-cell function. (rcsb.org)
  • Adenine deaminase activity was detected at low levels. (asm.org)
  • Adenine nucleosides and nucleotides are deaminated by adenosine deaminase and AMP deaminase to their corresponding inosine derivatives which, in turn, may be further degraded. (rcsb.org)
  • it is inactivated by a pyrimidine nucleoside deaminase, which converts it to the nontoxic uracil derivative. (nih.gov)
  • Gemcitabine (Figure 1, figure taken from ChEBI ), a synthetic pyrimidine nucleoside antimetabolite anticancer agent with complex metabolic pathways, is a group of chemotherapy drug. (ebi.ac.uk)
  • Extracellularly, a small fraction is also catabolized via a pathway mediated by pyrimidine nucleoside phosphorylase. (ebi.ac.uk)
  • SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug used presently as a standard of care. (aacrjournals.org)
  • AMP Deaminase Inhibitors. (patentgenius.com)
  • Concomitant adenosine deaminase inhibitors (eg, pentostatin): not recommended. (empr.com)
  • This provides the opportunity to use adenosine deaminase inhibitors as anticancer drugs. (thefreedictionary.com)
  • Treatment of african trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model. (thefreedictionary.com)
  • In principle, the above nucleotides and/or their nucleoside and nucleobase precursors can be obtained in several ways: synthesis de novo , direct acquisition by salvage or by subsequent interconversions to yield the appropriate repertoire of purines and pyrimidine derivatives found in the nucleic acids and other important molecular species. (pubmedcentralcanada.ca)
  • Cytidine as well as adenosine, thymidine, guanosine and uridine are one of the five standard nucleosides with which nucleic acids are composed. (abcam.com)
  • Here we describe for the first time the successful transformation of C. sporogenes, a clostridial strain with the highest reported tumor colonization efficiency, with the E. coli cytosine deaminase (CD) gene and show that systemically injected spores of these bacteria express CD only in the tumor. (nih.gov)
  • Gene therapy for human hepatocellular carcinoma with cytosine deaminase gene and prodrug flucytosine. (biomedsearch.com)
  • AIM: To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 5-fluorocytosine) on human hepatocellular carcinoma. (biomedsearch.com)
  • Metabolic pathways of purine (red) and pyrimidine (green) nucleotide degradation, via the nucleoside and base to the respective metabolic end products (blue), indicating the enzymes (pink) deficient in genetic disorders affecting these pathways. (els.net)
  • Surprisingly, P. putida lacks several salvage enzymes including nucleoside kinases, uridine phosphorylase and cytidine deaminase. (unt.edu)
  • 4 Degradation of adenosine by the enzymes adenosine deaminase and adenosine kinase, however, is confined to the intracellular compartment. (bmj.com)
  • Myoadenylate deaminase catalyses the reaction from adenosine monophosphate (AMP) to inosine monophosphate (IMP) plus ammonia (NH 3 ). (wiley.com)
  • Adenosine, guanosine, and inosine phosphorylase activities were detected for the conversion of base to nucleoside. (asm.org)
  • Nucleoside kinase activities for the conversion of adenosine, guanosine, and inosine to the respective nucleotides were detected by a new assay. (asm.org)
  • In a comprehensive mutant analysis involving single and multiple mutants of urate oxidase, xanthine dehydrogenase, nucleoside hydrolases, guanosine deaminase, and hypoxanthine guanine phosphoribosyltransferase, we demonstrate that purine nucleotide catabolism in Arabidopsis ( Arabidopsis thaliana ) mainly generates xanthosine, but not inosine and hypoxanthine, and that xanthosine is derived from guanosine deamination and a second source, likely xanthosine monophosphate dephosphorylation. (plantcell.org)
  • A drug that interferes with the action of the enzyme adenosine deaminase necessary for the irreversible conversion of adenosine to inosine. (thefreedictionary.com)
  • Failure to form inosine leads to abnormalities in purine nucleoside metabolism that are toxic to the cell concerned. (thefreedictionary.com)
  • Adenosine Deaminase from bovine spleen has been used in the immobilization on biostrip for stability and catalytic studies. (sigmaaldrich.com)
  • Gran C, Boyum A, Johansen RF, Lovhaug D, Seeberg EC: Growth inhibition of granulocyte-macrophage colony-forming cells by human cytidine deaminase requires the catalytic function of the protein. (hmdb.ca)
  • The self editing site of dADAR is found within exon 7 of the pre-mRNA, 3' to the second catalytic motif of the deaminase domain. (bl.uk)
  • My results confirm the hypothesis that the catalytic deaminase domain acquired dsRBMs, increasing the efficiency of the editing reaction on dsRNA. (bl.uk)
  • The dsRBMs bind non-specifically to dsRNA altering and stabilising the structure, allowing the catalytic domain easier access to the adenosine nucleoside to be edited. (bl.uk)
  • Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene. (wikipedia.org)
  • Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias. (wikipedia.org)
  • Demontis S, Terao M, Brivio M, Zanotta S, Bruschi M, Garattini E: Isolation and characterization of the gene coding for human cytidine deaminase. (hmdb.ca)
  • CDA (Cytidine Deaminase) is a Protein Coding gene. (genecards.org)
  • This gene encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. (genecards.org)
  • PNP (Purine Nucleoside Phosphorylase) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include drug binding and nucleoside binding . (genecards.org)
  • High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria. (thefreedictionary.com)
  • The PNP gene provides instructions for making an enzyme called purine nucleoside phosphorylase. (medlineplus.gov)
  • Mutations in the PNP gene reduce or eliminate the activity of purine nucleoside phosphorylase. (medlineplus.gov)
  • Autosomal recessive inheritance of two mutations in the adenosine deaminase gene was demonstrated. (portlandpress.com)
  • Whereas the antiviral activity and the preparation of purine nucleoside analogs which have an acyclic radical in position 9 have been known for a long time (see, for example, DE-A 2539963 or K. K. Ogilvie et al. (google.com)
  • Dr. Fernando Cabanillas reviews the role of pentostatin and other purine nucleoside analogs in the management of indolent NHL. (cancernetwork.com)
  • Without a functional nucleoside kinase, it was impossible to feed exogenous uridine to P. putida. (unt.edu)
  • Cytidine Deaminase Assay Kit (ab239723) uses Cytidine Deaminase (CDA) to convert cytidine to uridine and NH 3 , as intermediates. (abcam.com)
  • Cytidine Deaminase (3.5.4.5) is a homotetramer enzyme that catalyzes the irreversible deamination of cytidine to produce uridine, thus maintaining the intracellular pyrimidine pool of uridine. (abcam.com)
  • Note that the conversion of nucleotides and nucleosides can also be catalyzed by phosphotransferases (data not shown) transferring phosphate from a donor mononucleotide onto an acceptor nucleoside. (plantcell.org)
  • Also, 5'-nucleotidase catalyses the conversion of nucleotides to nucleosides and inhibits nucleoside kinases. (lclabs.com)
  • After passage through the cell membrane via nucleoside transporters, gemcitabine undergoes complex intracellular conversion to gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP). (lclabs.com)
  • Intracellular localization of human cytidine deaminase. (wikipedia.org)
  • It appears that the cytotoxic effect of pentostatin is independent of intracellular concentrations of adenosine deaminase. (cancernetwork.com)
  • Pentostatin (Nipent) is a nucleoside analog that inhibits the activity of the enzyme adenosine deaminase. (cancernetwork.com)
  • Therapeutic application of these oxetane compounds toward the treatment of nucleoside analog related disorders such as disorders involving cellular proliferation and infection are also described. (patentgenius.com)
  • 5-Fluoro-2-deoxycytidine (FdCyd), a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. (clinicaltrials.gov)
  • Gemcitabine is a nucleoside analog of deoxycytidine used as chemotherapy to treat patients with various types of cancer. (lclabs.com)
  • Amdoxovir, a guanosine nucleoside analog, is a prodrug deaminated by adenosine deaminase to 9-(β-D-1,3-dioxolan-4-yl)guanine (DXG). (nih.gov)
  • Another hallmark of DBA is the upregulation of adenosine deaminase (ADA), indicating changes in nucleotide metabolism. (biologists.org)
  • In 1975, Giblett and colleagues ( 4 ) reported a patient with an isolated T cell immunodeficiency who lacked activity of purine nucleoside phosphorylase, an enzyme situated between ADA and HPRT in the purine salvage pathway, providing convincing evidence of the critical importance of normal purine metabolism for a functioning immune system. (jimmunol.org)
  • Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. (diva-portal.org)
  • We observed altered in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside analogues, and a decrease in global DNA methylation in cells carrying both CDA variant alleles. (diva-portal.org)
  • Here we used CRISPR-Cas9 mutagenesis to show that phagocyte intoxication involves uptake of dAdo via the human equilibrative nucleoside transporter 1, dAdo conversion to dAMP by deoxycytidine kinase and adenosine kinase, and signaling via subsequent dATP formation to activate caspase-3-induced cell death. (pnas.org)
  • Studies to date suggest 2 transporters from each of the human concentrative nucleoside transporter family (hCNT1, hCNT3) and the equilibrative nucleoside transporter family (hENT1, hENT2) are capable of translocating gemcitabine across the cell surface ( 3 , 6 , 7-10 ). (aacrjournals.org)
  • Adenosine deaminase is a potential target for treatments of combined immunodeficiency disease. (sigmaaldrich.com)
  • In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). (springer.com)
  • The pyrimidine nucleosides are then taken up by tissues expressing the relevant kinases. (els.net)
  • Distribution of kinase and deaminase of 1-beta-D-arabinofuranosylcytosine in tissues of man and mouse. (semanticscholar.org)
  • It appears that the balance of kinase and deaminase levels may be an important factor in determining sensitivity or resistance of the cell to cytarabine. (nih.gov)
  • Adenosine deaminase is a purine catabolic enzyme which catalyzes the deamination of adenosine and 2′-deoxyadenosine with approximately equal specificity. (sigmaaldrich.com)
  • The deamination rate of 2',3'-isopropylidene adenosine catalyzed by adenosine deaminase (ADA) from calf intestine and adenylate deaminase (AMPDA) from Aspergillus species has been evaluated and compared with that of the enzymatic reactions of adenosine, to elucidate the influence of the protecting group on enzyme activity. (nih.gov)
  • Deamination of cytidines was first discovered in the mRNA encoding apolipoprotein B which is deaminated by Apobec1 a member of the apobec/AID cytidine deaminase family that mostly target cytidines in DNA. (frontiersin.org)
  • Adenosine deamination by adenosine deaminases that act on RNA (ADAR) seemingly only affects metazoan nuclear encoded RNAs. (frontiersin.org)
  • an enzyme causing deamination, or removal of an amino group from organic compounds, named according to its substrate as adenosine deaminase, cytidine deaminase, guanine deaminase, etc. (thefreedictionary.com)
  • Heat-induced formation of alpha,beta-unsaturated nucleoside dialdehydes and their activity with adenosine deaminase. (nih.gov)
  • One infant had purine nucleoside phosphorylase (PNP) activity in the leucocytes only half that of normal. (bmj.com)
  • The muscle biopsies were analysed for AMPD activity, purine nucleotides/nucleosides and bases, creatine, phosphocreatine, amino acids, and the TCA cycle intermediates malate, citrate and fumarate. (wiley.com)
  • The kit measures total Activity of Adenosine Deaminase with limit of quantification 1 mU recombinant Adenosine Deaminase. (biovision.com)
  • Guanine deaminase activity was not detected. (asm.org)
  • Variegate porphyria with coexistent decrease in porphobilinogen deaminase activity. (thefreedictionary.com)
  • At these time points, the activity of adenosine deaminase was measured in isolated lymphocytes, and forearm blood flow (FBF) was determined by venous occlusion plethysmography during administration of adenosine and dipyridamole into the brachial artery. (bmj.com)
  • PNP is highly specific for 6-oxopurine nucleosides and exhibits negligible activity for 6-aminopurine nucleosides. (rcsb.org)
  • However, because the deaminase domain has activity on its own it too must play a role in binding to dsRNA substrates. (bl.uk)
  • Estimation of Cytidine Deaminase Activity in mouse (26 µg) and rat (20 µg) kidney tissues. (abcam.com)
  • Nucleosides accumulate or are recycled from salvage pathways within the cell and play an important role in DNA and RNA synthesis and subsequent cell division. (abcam.com)
  • This compound belongs to the class of organic compounds known as purine nucleosides. (drugbank.ca)
  • Lipophilic, acid-stable, adenosine deaminase-activated anti-HIV prodrugs for central nervous system delivery. (nih.gov)
  • Use of 5-fluorodeoxycytidine and tetrahydrouridine to exploit high levels of deoxycytidylate deaminase in tumors to achieve DNA- and target-directed therapies. (semanticscholar.org)
  • In view of the 20- to 80-fold elevation of deoxycytidine-5'-phosphate (dCMP) deaminase in many human malignant tumors, we have utilized 5-fluorodeoxycytidine ( FdCyd ) coadministered with tetrahydrouridine ( H4Urd ) as a combination of antitumor agents against two murine solid tumors which possess high levels of dCMP deaminase. (semanticscholar.org)
  • Human cytidine deaminase (CDA) is an enzyme prominent for its role in catalyzing metabolic processing of nucleoside-type anticancer and antiviral agents. (rcsb.org)
  • In contrast to previously reported 2′-arabino modified nucleosides and EdU, F- ara -EdU causes little or no cellular arrest or DNA synthesis inhibition. (pnas.org)
  • Therefore, we treated RP-deficient zebrafish embryos with exogenous nucleosides and observed decreased activation of p53 and AMPK, reduced apoptosis, and rescue of hematopoiesis. (biologists.org)