Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Tosyllysine Chloromethyl Ketone: An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.Tosylphenylalanyl Chloromethyl Ketone: An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.KetonesBis(Chloromethyl) Ether: A substance that is an irritant to the eyes and respiratory tract and may be carcinogenic.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Ketone Bodies: The metabolic substances ACETONE; 3-HYDROXYBUTYRIC ACID; and acetoacetic acid (ACETOACETATES). They are produced in the liver and kidney during FATTY ACIDS oxidation and used as a source of energy by the heart, muscle and brain.Isoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Anhydrides: Chemical compounds derived from acids by the elimination of a molecule of water.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis.Dansyl Compounds: Compounds that contain a 1-dimethylaminonaphthalene-5-sulfonyl group.Absenteeism: Chronic absence from work or other duty.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Kinetics: The rate dynamics in chemical or physical systems.Amino Acid Sequence: 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.Pyroglutamyl-Peptidase I: An enzyme that catalyzes the release of a N-terminal pyroglutamyl group from a polypeptide provided the next residue is not proline. It is inhibited by thiol-blocking reagents and occurs in mammalian tissues, microorganisms, and plants. (From Enzyme Nomenclature, 1992) EC 3.4.19.3.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.p-Chloromercuribenzoic Acid: An organic mercurial used as a sulfhydryl reagent.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Molecular Weight: The sum of the weight of all the atoms in a molecule.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Tosyl CompoundsTrypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Treponema: A genus of microorganisms of the order SPIROCHAETALES, many of which are pathogenic and parasitic for man and animals.Caloric Restriction: Reduction in caloric intake without reduction in adequate nutrition. In experimental animals, caloric restriction has been shown to extend lifespan and enhance other physiological variables.Molecular Sequence Data: 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.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Cycloparaffins: Alicyclic hydrocarbons in which three or more of the carbon atoms in each molecule are united in a ring structure and each of the ring carbon atoms is joined to two hydrogen atoms or alkyl groups. The simplest members are cyclopropane (C3H6), cyclobutane (C4H8), cyclohexane (C6H12), and derivatives of these such as methylcyclohexane (C6H11CH3). (From Sax, et al., Hawley's Condensed Chemical Dictionary, 11th ed)Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Porphyromonas gingivalis: A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium produces a cell-bound, oxygen-sensitive collagenase and is isolated from the human mouth.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cloning, Molecular: 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.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Oligopeptides: Peptides composed of between two and twelve amino acids.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Bacteroides: A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Protein PrecursorsAmino Acids, Essential: Amino acids that are not synthesized by the human body in amounts sufficient to carry out physiological functions. They are obtained from dietary foodstuffs.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Methyl n-Butyl Ketone: An industrial solvent which causes nervous system degeneration. MBK is an acronym often used to refer to it.Amino Acid Transport Systems: Cellular proteins and protein complexes that transport amino acids across biological membranes.Acetoacetates: Salts and derivatives of acetoacetic acid.Sequence Alignment: 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.3-Hydroxybutyric Acid: BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Amino Acid Motifs: 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.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Escherichia coli: 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.Mutation: 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.

Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. (1/1161)

Apoptosis was induced in human glioma cell lines by exposure to 100 nM calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (2/1161)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

Anti-apoptotic role of telomerase in pheochromocytoma cells. (3/1161)

Telomerase is a protein-RNA enzyme complex that adds a six-base DNA sequence (TTAGGG) to the ends of chromosomes and thereby prevents their shortening. Reduced telomerase activity is associated with cell differentiation and accelerated cellular senescence, whereas increased telomerase activity is associated with cell transformation and immortalization. Because many types of cancer have been associated with reduced apoptosis, whereas cell differentiation and senescence have been associated with increased apoptosis, we tested the hypothesis that telomerase activity is mechanistically involved in the regulation of apoptosis. Levels of telomerase activity in cultured pheochromocytoma cells decreased prior to cell death in cells undergoing apoptosis. Treatment of cells with the oligodeoxynucleotide TTAGGG or with 3,3'-diethyloxadicarbocyanine, agents that inhibit telomerase activity in a concentration-dependent manner, significantly enhanced mitochondrial dysfunction and apoptosis induced by staurosporine, Fe2+ (an oxidative insult), and amyloid beta-peptide (a cytotoxic peptide linked to neuronal apoptosis in Alzheimer's disease). Overexpression of Bcl-2 and the caspase inhibitor zVAD-fmk protected cells against apoptosis in the presence of telomerase inhibitors, suggesting a site of action of telomerase prior to caspase activation and mitochondrial dysfunction. Telomerase activity decreased in cells during the process of nerve growth factor-induced differentiation, and such differentiated cells exhibited increased sensitivity to apoptosis. Our data establish a role for telomerase in suppressing apoptotic signaling cascades and suggest a mechanism whereby telomerase may suppress cellular senescence and promote tumor formation.  (+info)

Monocytic cell necrosis is mediated by potassium depletion and caspase-like proteases. (4/1161)

Apoptosis is a physiological cell death that culminates in mitochondrial permeability transition and the activation of caspases, a family of cysteine proteases. Necrosis, in contrast, is a pathological cell death characterized by swelling of the cytoplasm and mitochondria and rapid plasma membrane disruption. Necrotic cell death has long been opposed to apoptosis, but it now appears that both pathways involve mitochondrial permeability transition, raising the question of what mediates necrotic cell death. In this study, we investigated mechanisms that promote necrosis induced by various stimuli (Clostridium difficile toxins, Staphylococcus aureus alpha toxin, ouabain, nigericin) in THP-1 cells, a human monocytic cell line, and in monocytes. All stimuli induced typical features of necrosis and triggered protease-mediated release of interleukin-1beta (IL-1beta) and CD14 in both cell types. K+ depletion was actively implicated in necrosis because substituting K+ for Na+ in the extracellular medium prevented morphological features of necrosis and IL-1beta release. N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad-spectrum caspase inhibitor, prevented morphological features of necrosis, plasma membrane destruction, loss of mitochondrial membrane potential, IL-1beta release, and CD14 shedding induced by all stimuli. Thus, in monocytic cells, necrosis is a cell death pathway mediated by passive K+ efflux and activation of caspase-like proteases.  (+info)

Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro. (5/1161)

Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein of unknown physiological function. The mechanism of Lp(a) atherogenicity as well as its catabolic pathways are only incompletely understood at present. In this report, we show that the low density lipoprotein receptor (LDLR) gene family member megalin/glycoprotein (gp) 330 is capable of binding and mediating the cellular uptake and degradation of Lp(a) in vitro. A mouse embryonic yolk sac cell line with native expression of megalin/gp330 but genetically deficient in LDLR-related protein (LRP) and a control cell line carrying a double knockout for both LRP and megalin/gp330 were compared with regard to their ability to bind, internalize, and degrade dioctadecyltetramethylindocarbocyanine perchlorate (DiI)-fluorescence-labeled Lp(a) as well as equimolar amounts of 125I-labeled Lp(a) and LDL. Uptake and degradation of radiolabeled Lp(a) by the megalin/gp330-expressing cells were, on average, 2-fold higher than that of control cells. This difference could be completely abolished by addition of the receptor-associated protein, an inhibitor of ligand binding to megalin/gp330. Mutual suppression of the uptake of 125I-Lp(a) and of 125I-LDL by both unlabeled Lp(a) and LDL suggested that Lp(a) uptake is mediated at least partially by apolipoprotein B100. Binding and uptake of DiI-Lp(a) resulted in strong signals on megalin/gp330-expressing cells versus background only on control cells. In addition, we show that purified megalin/gp330, immobilized on a sensor chip, directly binds Lp(a) in a Ca2+-dependent manner with an affinity similar to that for LDL. We conclude that megalin/gp330 binds Lp(a) in vitro and is capable of mediating its cellular uptake and degradation.  (+info)

Caspase-dependent activation of calpain during drug-induced apoptosis. (6/1161)

We have previously demonstrated that calpain is responsible for the cleavage of Bax, a proapoptotic protein, during drug-induced apoptosis of HL-60 cells (Wood, D. E., Thomas, A., Devi, L. A., Berman, Y., Beavis, R. C., Reed, J. C., and Newcomb, E. W. (1998) Oncogene 17, 1069-1078). Here we show the sequential activation of caspases and calpain during drug-induced apoptosis of HL-60 cells. Time course experiments using the topoisomerase I inhibitor 9-amino-20(S)-camptothecin revealed that cleavage of caspase-3 substrates poly(ADP-ribose) polymerase (PARP) and the retinoblastoma protein as well as DNA fragmentation occurred several hours before calpain activation and Bax cleavage. Pretreatment with the calpain inhibitor calpeptin blocked calpain activation and Bax cleavage but did not inhibit PARP cleavage, DNA fragmentation, or 9-amino-20(S)-camptothecin-induced morphological changes and cell death. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited PARP cleavage, DNA fragmentation, calpain activation, and Bax cleavage and increased cell survival by 40%. Interestingly, Z-VAD-fmk-treated cells died in a caspase- and calpain-independent manner that appeared morphologically distinct from apoptosis. Our results suggest that excessive or uncontrolled calpain activity may play a role downstream of and distinct from caspases in the degradation phase of apoptosis.  (+info)

Essential role of caspase-3 in apoptosis of mouse beta-cells transfected with human Fas. (7/1161)

Several recent studies have indicated that the Fas-Fas ligand system may be critical for pancreatic beta-cell destruction in type 1 diabetes. Although the fundamental roles of caspases in the mammalian apoptotic machinery have been elucidated, it is not known which caspase or caspases play a major role in Fas-mediated apoptosis of beta-cells. In this study, we transfected human Fas cDNA into a mouse beta-cell line (betaTC1) and established a beta-cell clone expressing human Fas. This clone, designated hFas/betaTC1, underwent apoptosis when exposed to anti-Fas, showing hallmarks of apoptosis (chromatin condensation, nucleolar disintegration, internucleosomal DNA fragmentation, and annexin V staining), indicating that the mouse beta-cell line has the intact machinery of Fas-mediated apoptosis. The cross-linking of Fas by anti-Fas resulted in the elevation of caspase-3-like, but not caspase-1-like, protease activity 2-12 h after the addition of the anti-Fas. A caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, attenuated the Fas-mediated beta-cell apoptosis, while a caspase-1 inhibitor, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, failed to suppress the apoptosis. Thus the Fas-induced death signal apparently bypassed caspase-1 in the cells. Furthermore, an antisense caspase-3 construct blocked caspase-3 activation and substantially suppressed Fas-triggered apoptosis of hFas/betaTC1 cells. These observations suggest the essential role of caspase-3 in Fas-mediated apoptosis of the beta-cell line.  (+info)

The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event. (8/1161)

During apoptosis induced by various stimuli, cytochrome c is released from mitochondria into the cytosol where it participates in caspase activation. This process has been proposed to be an irreversible consequence of mitochondrial permeability transition pore opening, which leads to mitochondrial swelling and rupture of the outer mitochondrial membrane. Here we present data demonstrating that NGF-deprived sympathetic neurons protected from apoptosis by caspase inhibitors possess mitochondria which, though depleted of cytochrome c and reduced in size, remained structurally intact as viewed by electron microscopy. After re-exposure of neurons to NGF, mitochondria recovered their normal size and their cytochrome c content, by a process requiring de novo protein synthesis. Altogether, these data suggest that depletion of cytochrome c from mitochondria is a controlled process compatible with function recovery. The ability of sympathetic neurons to recover fully from trophic factor deprivation provided irreversible caspase inhibitors have been present during the insult period, has therapeutical implications for a number of acute neuropathologies.  (+info)

*Tosyl phenylalanyl chloromethyl ketone

The phenylalanine moiety is bound to the enzyme because of specificity for aromatic amino acid residues at the active site (as ... Tosyl phenylalanyl chloromethyl ketone (TPCK) is a protease inhibitor. Its structural formula is 1-chloro-3-tosylamido-4-phenyl ... The chloromethyl group reacts with the active site cysteine to form a covalent bond with the loss of the chlorine. TPCK is ...

*Degradomics

TAILS is also compatible with Stable isotope labeling by amino acids in cell culture (SILAC). COFRADIC was the earliest ... Zymogen/enzyme discrimination using peptide chloromethyl ketones J. Biol. Chem., 264 (13) 7536-7545 (1989). Kidd D., Liu Y., ... Standard peptides synthesized from amino acids labeled with stable isotope atoms serve as internal standards for serial ... enzymatic activity profiling in complex proteomes Amino Acids, 30 (4) 333-350 (2006). Greenbaum D.C., Baruch A., Grainger M., ...

*Trypsin

... cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when either is ... The activity of trypsin is not affected by the enzyme inhibitor tosyl phenylalanyl chloromethyl ketone, TPCK, which deactivates ... This means that trypsin predominantly cleaves proteins at the carboxyl side (or "C-terminal side") of the amino acids lysine ... The peptide products are then further hydrolyzed into amino acids via other proteases, rendering them available for absorption ...

*List of extremely hazardous substances

... ester Phosphonothioic acid, methyl-, S-(2-(bis(1-methylethyl)amino)ethyl) O-ethyl ester Phosphonothioic acid, methyl-, O-(4- ... chloromethyl) ketone Bitoscanate Boron trichloride Boron trifluoride Boron trifluoride compound with methyl ether (1:1) ... Chlormequat chloride Chloroacetic acid 2-chloroethanol Chloroethyl chloroformate Chloroform Chloromethyl ether Chloromethyl ... 4-amino- Pyridine, 4-nitro-, 1-oxide Pyriminil Ricin Salcomine Sarin Selenious acid Semicarbazide hydrochloride Silane, (4- ...

*Insertion reaction

... diazomethane methylene group is inserted into the carbon-chlorine bond of an acid chloride to generate an α-chloromethyl ketone ... Organic Syntheses provides the example of t-BOC protected (S)-phenylalanine (2-amino-3-phenylpropanoic acid) being reacted ... 3-amino-4-phenylbutanoic acid. Mechanistically, the α-diazoketone undergoes a Wolff rearrangement to form a ketene in a 1,2- ... a methylene unit is inserted into the carboxyl-carbon bond of carboxylic acid to form the next acid in the homologous series. ...

*Knorr pyrrole synthesis

The mechanism requires zinc and acetic acid as catalysts. It will proceed at room temperature. Because α-amino-ketones self- ... The 5-methyl group can be variously oxidized to chloromethyl, aldehyde, or carboxylic acid functionality by the use of ... The method involves the reaction of an α-amino-ketone (1) and a compound containing an electron-withdrawing group (e.g. an ... and tertiary-butyl groups can be removed by treatment with trifluoroacetic acid, or boiling aqueous acetic acid. R1 and R3 (as ...

*Homologation reaction

... chloromethyl ketone formation (4) with hydrochloric acid, organic reduction of chlorine to methylketone (5), ketone ... Has been used to convert β-amino esters from α-amino esters through an ynolate intermediate. Seyferth-Gilbert homologation in ... pyruvic acid is removed from a linear aliphatic carboxylic acid yielding a new acid with 2 carbon atoms less. The original ... Arndt-Eistert reaction is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic acid ...

*Proteinase K

... iodoacetic acid, EDTA or by other serine protease inhibitors like Nα-Tosyl-Lys Chloromethyl Ketone (TLCK) and Nα-Tosyl-Phe ... the enzyme digests proteins preferentially after hydrophobic amino acids (aliphatic, aromatic and other hydrophobic amino acids ... Jany KD, Lederer G, Mayer B (1986). "Amino acid sequence of proteinase K from the mold Tritirachium album Limber". FEBS Lett. ... of cleavage is the peptide bond adjacent to the carboxyl group of aliphatic and aromatic amino acids with blocked alpha amino ...

*Plasma kallikrein

... and trypsin with amino acid and peptide thioesters: development of new sensitive substrates". Biochemistry. 20: 7196-7206. doi: ... "Synthesis of tripeptide chloromethyl ketones and examination of their inhibitory effects on plasmin and plasma kallikrein". ...

*List of MeSH codes (D12.125)

... tosylphenylalanyl chloromethyl ketone MeSH D12.125.067.500 --- aspartic acid MeSH D12.125.067.500.150 --- d-aspartic acid MeSH ... 2-amino-5-phosphonovalerate MeSH D12.125.072.050 --- amino acids, aromatic MeSH D12.125.072.050.342 --- dextrothyroxine MeSH ... 2-aminoadipic acid MeSH D12.125.119.170 --- aspartic acid MeSH D12.125.119.170.150 --- d-aspartic acid MeSH D12.125.119.170.275 ... glutamic acid MeSH D12.125.067.750.150 --- 1-carboxyglutamic acid MeSH D12.125.067.750.400 --- glutamates MeSH D12.125.067.750. ...

*Organosilicon

Other unsaturated functional groups-alkynes, imines, ketones, and aldehydes. An example is the hydrosilation of phenylacetylene ... Synthesis and Structure of a Base-Stabilized C-Phosphino-Si-Amino Silyne. Angewandte Chemie International Edition, 49: 6585- ... chloromethyl)silane, trichloro(dichlorophenyl)silane, trichloroethylsilane, and phenyltrichlorosilane. Although proportionately ... reaction for the synthesis of this compound class is by heating hexaalkyldisiloxanes R3SiOSiR3 with concentrated sulfuric acid ...

*List of MeSH codes (D02)

... tosyllysine chloromethyl ketone MeSH D02.455.426.559.389.832.710 --- tosylphenylalanyl chloromethyl ketone MeSH D02.455.426.559 ... trinitrobenzenesulfonic acid MeSH D02.640.600.200 --- 5-amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole MeSH D02.640.600.290 ... tosyllysine chloromethyl ketone MeSH D02.886.590.887.660 --- tosylphenylalanyl chloromethyl ketone MeSH D02.886.640.150 --- ... edetic acid MeSH D02.241.081.038.455 --- egtazic acid MeSH D02.241.081.038.581 --- iodoacetic acid MeSH D02.241.081.038.581.400 ...
Z-VAD(OMe)-FMK is a cell permeable peptide which binds irreversibly to the catalytic site of intracellular enzymes known as caspases, which play an important role in the induction of apoptosis. The binding of Z-VAD(OMe)-FMK to caspases inhibits the acti
The Ac-YVAD-cmk and Ac-DEVD-CHO peptide inhibitors block TRAIL-induced DNA fragmentation in mouse and human cells. (A) Soluble DNA was extracted from mouse my
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Ac-YVAD-CMK | Ac-Tyr-Val-Ala-Asp-CH2Cl Ac-YVAD-Chloromethylketone3180-v 5 mg | 165.00 EUR Acetyl- L-tyrosyl- L-valyl- L-alanyl- ...
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References for Abcams pan Caspase (active) Red Staining Kit (ab65616). Please let us know if you have used this product in your publication
购买Z-LE(OMe)VD(OMe)-FMK,具有细胞渗透性的Z-LEVD-FMK caspase-4抑制剂 derivative。使用Abcam高品质的Z-LE(OMe)VD(OMe)-FMK帮助您更快取得科研成果。
Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.
zVAD-fmk does not totally abrogate FasL-triggered apoptosis in HeLa cells expressing caspase-10 at low level.A, B, Casp10+ and Casp10- HeLa cells were incubated
BACKGROUND: Programmed necrosis/necroptosis is an emerging form of cell death that plays important roles in mammalian development and the immune system. The pro-necrotic kinases in the receptor interacting protein (RIP) family are crucial mediators of programmed necrosis. Recent advances in necrosis research have been greatly aided by the identification of chemical inhibitors that block programmed necrosis. Necrostatin-1 (Nec-1) and its derivatives were previously shown to target the pro-necrotic kinase RIP1/RIPK1. The protective effect conferred by Nec-1 and its derivatives in many experimental model systems was often attributed to the inhibition of RIP1 function. METHODOLOGY/PRINCIPAL FINDINGS: We compared the effect of Nec-1 and siRNA-mediated silencing of RIP1 in the murine fibrosarcoma cell line L929. Treatment of L929 cells with the pan-caspase inhibitor zVAD-fmk or exogenous TNF induces necrosis. Strikingly, we found that siRNA-mediated silencing of RIP1 inhibited zVAD-fmk induced necrosis, but
Poster (2015, June 14). Study question: In a model reproducing early ischemia after ovarian tissue transplantation, does the pan-caspase inhibitor Z-VAD-FMK could prevent granulosa cell apoptosis? Summary answer: Results ... [more ▼]. Study question: In a model reproducing early ischemia after ovarian tissue transplantation, does the pan-caspase inhibitor Z-VAD-FMK could prevent granulosa cell apoptosis? Summary answer: Results obtained with HGL5 granulosa cell line suggest that Z-VAD-FMK is efficient to protect granulosa cells from etoposide or CoCl2 induced apoptosis. What is known already: Removal, cryopreservation and subsequent graft of ovarian strips after cancer treatment have been successfully used to re-establish female fertility. However, the pregnancy rate after autografting of cryopreserved tissue is about 30%. Indeed, the major problem after transplantation is follicular loss due to ischemic reperfusion injury. Study design, size, duration: Three human granulosa cell lines (GC1a, ...
dansylglutamyl-glycyl-arginine chloromethyl ketone | C26H36ClN7O7S | CID 122261 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
98833-79-5 - YHBCRLLVTTVQMA-IKGGRYGDSA-N - Tyrosyl-prolyl-arginyl chloromethyl ketone - Similar structures search, synonyms, formulas, resource links, and other chemical information.
Caspase inhibition is effective in minimizing nucleosome accumulation in key cortical cultures stimulated by TNF and thrombin. In contrast, the exact same effect is simply not observed in differentiated PC12 cells. In PC12 cells TNF induced LDH release is decreased by caspase inhibition. For the reason that TNF remedy induces both LDH release and nucleosome accumulation in PC12 cells, caspase inhibition could possibly enrich cell survival below disorders that induce a mixed apoptotic necrotic response. Pytlowany and colleagues demonstrate that In PC12 cells NO released from SNP decreases cell viability inside a time and concentration dependent method, with a increased concentration of NO leading to immediate and sustained lower in cell survival with no evoking a corresponding immediate activation of caspase three . In the recent review we locate that NO created by 0.5 mM SNP activates caspase three inside a longer time frame ...
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The use of caspase inhibitors has revealed the existence of alternative backup cell death programs for apoptosis. The broad-spectrum caspase inhibitor zVAD-fmk modulates the three major types of cell death. Addition of zVAD-fmk blocks apoptotic cell death, sensitizes cells to necrotic cell death, and induces autophagic cell death. Several studies have shown a crucial role for the kinase RIP1 and the adenosine nucleotide translocator (ANT)-cyclophilin D (CypD) complex in necrotic cell death. The underlying mechanism of zVAD-fmk-mediated sensitization to necrotic cell death involves the inhibition of caspase-8-mediated proteolysis of RIP1 and disturbance of the ANT-CypD interaction. RIP1 is also involved in autophagic cell death. Caspase inhibitors and knockdown studies have revealed negative roles for catalase and caspase-8 in autophagic cell death. The positive role of RIP1 and the negative role of caspase-8 in both necrotic and autophagic cell death suggest that the pathways of these two types ...
Other names: mast cell protease I; skeletal muscle protease; skin chymotryptic proteinase; mast cell serine proteinase, chymase; skeletal muscle (SK) protease. Comments: In mast cell granules. In peptidase family S1 (trypsin family). Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 97501-92-3. References 1. Woodbury, R.G., Everitt, M. and Neurath, H. Mast cell proteases. Methods Enzymol. 80 (1981) 588-609. [PMID: 7043202]. 2. Powers, J.C., Tanaka, T., Harper, J.W., Minematsu, Y., Barker, L., Lincoln, D., Crumley, K.V., Fraki, J.E., Schechter, N.M., Lazarus, G.G., Nakajima, K., Nakashino, K., Neurath, H. and Woodbury, R.G. Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors. Biochemistry 24 (1985) 2048-2058. [PMID: 3893542]. 3. Johnson, L.A., Moon, K.E. and ...
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... ,Apoptosis is an evolutionarily conserved form of cell suicide, which follows a specialized cellular process. The central component of this process is a cascade of proteolytic enzymes called caspases. These enzymes participate in a series of reactions that are triggered in response to pro-apoptoti,biological,biology supply,biology supplies,biology product
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Aggregatibacter actinomycetemcomitans (Aa) expresses a 64-kDa GroEL protein belonging to the heat shock family of proteins. This protein has been shown to influence human host cells, but the apoptotic capacity of the GroEL protein regarding T cells is not yet known. The purpose of this study was to investigate the ability of A. actinomycetemcomitans GroEL (AaGroEL) protein to induce human peripheral blood T-cell apoptosis. Endogenous, purified AaGroEL protein was used as an antigen. In AaGroEL-treated T cells, the data indicated that phosphatidylserine exposure, an early apoptotic event, was dose- and time-dependent. The AaGroEL-treated T cells were also positive for active caspase-3 in a dose-dependent manner. The rate of AaGroEL-induced apoptosis was suppressed by the addition of the general caspase inhibitor Z-VAD-FMK. Furthermore, cleaved caspase-8 bands (40/36 kDa and 23 kDa) were identified in cells responding to AaGroEL. DNA fragmentation was also detected in the AaGroEL-treated T cells. ...
Glioblastoma multiforme is the most common brain tumors and have a worse prognosis, so it is needed to develop effective treatments. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, including 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and synthetic ligands, troglitazone and rosiglitazone, are known to sensitize tumor cells to apoptosis via various molecular mechanisms. In this study, we investigated the therapeutic potentials of combined treatment with PPAR-γ agonists and TRAIL in TRAIL-resistant astrocytoma cells. TRAIL alone and each PPAR-γ agonist exhibited no cytotoxic effects; while the pre-incubation with PPAR-γ agonists enhanced dramatically TRAIL-induced cell death, which was abrogated by a broad spectrum caspase inhibitor, z-VAD-fmk. And also, the combined treatment with PPAR-γ agonists and TRAIL increased the enzymatic activity of caspase-3. These results indicate that PPAR-γ agonists might promote TRAIL-mediated apoptosis by modulating the caspase activity. ...
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In Figure 3, they added the DRACOs to these cells, either with, or without the inhibitor. They also included a product which makes cells which have just self destructed glow in the dark. The first four sections on the graph are simply controls, to pick up the background levels of cell death. Since the main function of caspases is to cause cell death to occur, you can guess what would happen if we were to add caspase inhibitors to a normal set of cells. The blue and red bars are both lower than the green bar , because they have the caspase inhibitors added. The next three sections show what happens when DRACOs are added to the mix, and they show that they kill off a lot of cells. And importantly, you can tell that its performed using caspases, because in the presence of inhibitor, the cells do not die as much. In fact, the levels of death seen is more or less the same as the other controls with inhibitors ...
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4058 MDA-435 human breast cancer cells treated with staurosporine (STS) showed characteristic hallmarks of apoptotic death with nuclear condensation and apoptotic bodies in a dose and time-dependent manner. Evidence of activation of caspase 3, 7 and 10 appeared as early as 4 hours of STS treatment and was maximal at 2 and 4 ∈1/4 M STS. The pan-caspase inhibitor, zVAD-fmk, blocked the activation of these caspases. Activation of caspases 8 and 9 required higher STS concentrations or longer time. The BAG family of co-chaperone proteins has survival-promoting functions in cancer cells. Unexpectedly BAG-3/CAIR-1 and BAG-4/SODD, but not BAG-1, were partially or totally lost by the STS treatments. The effects were concomitant with caspase 3 activation, and the use of zVAD-fmk and that of several specific caspase inhibitors partially rescued the loss of BAG-3 and BAG-4. In cells over-expressing a BAG-3 mutant lacking the proline-rich (PXXP) domain, this protein was protected from STS-mediated ...
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Although DMSO is widely used in experimental systems due to its extraordinary solvent properties, it also exerts a number of biological effects that might not always be considered during experimental design. These effects include inhibition of APAP hepatic drug metabolism,26, 27 antioxidative activity,26-28 as well as adjuvant-like actions on the immune system.29-32 A recent example highlighting an unanticipated effect of DMSO was observed in a study testing the involvement of caspases, and possibly apoptosis, in AILI.20 In this study, a pancaspase inhibitor solubilized in 2.5% DMSO was administered to mice just prior to APAP treatment. The observed inhibition of AILI following treatment with this compound was subsequently discovered to be due apparently to the inhibition of APAP metabolism by DMSO rather than to the inhibition of caspases by the pancaspase inhibitor.20, 21. Our findings here illustrate another example where the use of DMSO has confounded the interpretation of experimental ...
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Here, we demonstrate that administration of a TLR3 agonist and pan-caspase inhibitor, zVAD, results in tumor regression in mice secondary to tumor cytolysis. Notably, direct action of these reagents on tumor cells induces a tumoricidal event. In the literature, activation of caspases usually accelerates programmed cell death, and prior polyI:C-mediated priming of TICAM-1 is crucial in promoting caspase-mediated inflammasome activation in lipopolysaccharide (LPS) signaling (19, 26). In contrast with the TICAM-1-inflammasome axis, which involves caspase-11 and effector caspases-3 and -7 (19, 31), the necrotic cell death observed in fibroblasts and macrophages is mainly induced through the TICAM-1-RIP3 pathway that involves no caspases (13): This pathway is activated in the absence of caspase-8 activity. This cell death process fits the definition of necroptosis, in which cell death is RIR1/3-dependent and can be inhibited by nec-1, and based on the production of ROS (4). We found this type of ...
3-(Chloromethyl)pyridine hydrochloride is an intermediate that has been proposed for use in the synthesis of agricultural, pharmaceutical, and veterinary chemicals.. A bioassay of 3-(chloromethyl)pyridine hydrochloride for possible carcinogenicity was conducted by administering the test chemical by gavage to Fischer 344 rats and B6C3F1 mice.. Groups of 50 rats and 50 mice of each sex were administered 3-(chloromethyl)pyridine hydrochloride in a vehicle of distilled water three times per week at one of the following doses, either 75 or 150 mg/kg body weight for the rats and either 100 or 200 mg/kg body weight for the mice. The low-dose rats were dosed for 103 weeks and the low-dose mice for 102 weeks. Because of early deaths in the high-dose animals, the high-dose rats were dosed for only 83 weeks and the high-dose mice for only 81 weeks. Controls consisted of groups of 20 rats and 20 mice of each sex which were administered the vehicle only for 104 weeks. All surviving rats and mice were killed ...
The registry of classification and labelling (CLH) intentions until outcome lists the intentions and proposals received by ECHA for a new or revised harmonised classification and labelling of a substance. The proposals are submitted by Member State competent authorities, manufacturers, importers or downstream users. Interested parties can follow the progress of a proposal through the CLH process, from the notification of the intention to the adoption of the opinion of the Committee for Risk Assessment (RAC). The advance notice enables interested parties to plan and prepare for commenting later on.. Anyone with relevant information on the identity or hazard properties of a substance is encouraged to provide this information to the dossier submitter during the early stages of the process, or at the latest during the public consultation.. Where an opinion has been adopted by RAC, the status is indicated as Opinion Adopted.. Note: The classification tables for those substances that have been ...
The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database ...
The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database ...
LB-18 compound: synthetic drug closely related to lembehyne-A (derived from a marine sponge) induces caspase-independent cell death to human neuroblastoma cells; structure in first source
Lucas C. Ducati.; Matheus P. Freitas.; Cláudio F. Tormena, Roberto Rittner. Conformational and stereoelectronic investigation of chloromethyl methyl sulfide and its sulfinyl and sulfonyl analogs. Journal of Molecular Structure. 2006, 800 (1-3), 45-50.. Akira Hosomi.; Shinji Hayashi.; Koichiro Hoashi.; Shinya Kohra.; Yoshinori Tominaga. Intramolecular cyclization via onium salts: a novel synthesis of 1,3-thiazolidines from chloromethyl (trimethylsilyl)methyl sulfide and nitrogen-containing heteroaromatic compounds. J. Org. Chem. 1987, 52 (19), 4423-4424.. Protects alcohols as their methylthiomethyl (MTM) ethers by reaction, e.g. with NaH/NaI in DME: Tetrahedron Lett., 3269 (1975), or with AgNO3/Et3N: Chem. Lett., 1277 (1979). MTM ethers are relatively stable to acid but can be cleaved selectively with HgCl2 in aqueous acetonitrile or AgNO3/ 2,6-lutidine: Tetrahedron Lett., 3269 (1975), by methylation (MeI) and hydrolysis: Austral. J. Chem., 31, 1031 (1978); Chem. Lett., 715 (1984), or with TMS ...
Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein (XIAP) against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by ...
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This phenomenon was noted to be parallel to the cell cycle arrest and the right shifting of the DNA profile in the cell cycle analysis. How To Use Kratom Extract Powder Forman these events only occurred at high doses of MSE or MIT. SH-SY5Y cells which are known to have wild-type p53 have constitutive expression of p53 in the control and lower doses groups.. The inhibitors used were caspase kratom free overnight shipping 3 inhibitor caspase 8 inhibitor caspase 9 inhibitor general caspase inhibitor negative control and doxorubicin as a positive control ( as described in section 5. The positive control doxorubicin confirmed the assay works by showing a highly significant response for apoptosis. Thus this kratom buy online uk finding supported the notion that How To Use Kratom Extract Powder Forman there was no involvement of caspase executioner nor caspase initiator activation in cell death induced by high dose MSE. C o N ntr eg ol a (E what is kratom tea parma M tive tO C M SE co H) a C sp.. DNA ...
The present study was designed to determine whether the p53 tumor-suppressor protein is involved in the development of antinociceptive tolerance to morphine. When the doses of morphine (mg/kg per injection) were subcutaneously given into mice as pretreatment twice daily for 2 days (first day (30) and second day (60)), intrathecal (i.t.) administration of morphine (0.1nmol) was inactive due to antinociceptive tolerance in the 0.5% formalin test on the third day. Tolerance to i.t. morphine was significantly suppressed by i.t. injection of pifithrin-alpha (1 and 10nmol), an inhibitor of p53 activation, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-fmk) (1 and 10nmol), a non-selective caspase inhibitor, or N(G)-nitro-l-arginine methyl ester (l-NAME) (2 and 20nmol), a non-selective inhibitor of nitric oxide synthase, 5min before each morphine treatment during the induction, with none given on the test day. Moreover, p53 expression in the spinal cord had increased significantly 14h ...
The synthesis of racemic Carvedilol ((±)-1) has been achieved starting from 2-(chloromethyl) oxirane ((±)-2) in a four-step sequence. 5-(Chloromethyl) oxazolidin-2-one ((±)-3) and 5-((9H-carbazol-4-yloxy) methyl) oxazolidin-2-one ((±)-4) are intermediates. A similar sequence starting from (R)- or (S)-2-(chloromethyl)oxirane 2 give corresponding chiral 5-((9H-carbazol-4-yloxy)methyl) oxazolidin-2-one 4 followed by chiral Carvedilol 1. The synthetic sequence followed avoids the formation of impurity B (bis impurity). This approach can be useful for the preparation of pharmaceutically important moieties containing β-amino alcohols without formation of bis impurity ...
Caspases play an important role in the ability of animal cells to kill themselves by apoptosis. Caspase activity is regulated in vivo by members of three distinct protease inhibitor families, two of which, baculovirus p35 and members of the inhibitor of apoptosis (IAP) family, are thought to be caspase specific. However, caspases are members of the clan of cysteine proteases designated CD, which also includes animal and plant legumains, and the bacterial proteases clostripain, gingipain-R and gingipain-K. Since these proteases have been proposed to have a common mechanism and evolutionary origin, we hypothesized that the caspase inhibitors may also regulate these other proteases. We tested this hypothesis by examining the effect of the natural caspase inhibitors on other members of protease clan CD. The IAP family proteins were found to have only a slight inhibitory effect on gingipain-R. The cowpox viral cytokine-response modifier A (CrmA) serpin had no effect on any of the proteases tested but ...
Paddenberg, P., Wulf, S., Weber, A., Heimann, P., Beck, L. A., & Mannherz, H. G. (1996). Internucleosomal DNA fragmentation in cultured cells under conditions reported to induce apoptosis may be caused by mycoplasma endonucleases. Eur J Cell Biol, 71(1), 105-119 ...
The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.
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Khat is the Celastraceus edulis plant, a flowering evergreen tree or large shrub, which grows in the Horn of Africa and southwestern Arabia. Khat use has been associated with development of oral cancer, but its molecular effects remain controversial. This study describes a novel cytotoxic effect of whole khat extract on three leukemia cell lines. Cells were exposed to khat extract and harvested for analysis by fluorescent and electron microscopy, trypan blue exclusion, as well as immunoblotting to characterize the mode of cell death. In a separate series, cells were pretreated with a panel of caspase inhibitors for possible inhibitory effects. Khat induced a rapid cell death effect in HL-60, Jurkat, and NB4 cells that occurred within 2 h of exposure. The treated cells retained their ability to exclude trypan blue dye, a key feature in the apoptotic process. Exposed cells consistently developed morphological features of manifest apoptosis. Z-VAD, a pan-caspase inhibitor, completely inhibited ...
EINECS (European INventory of Existing Commercial chemical Substances) as published in O.J. C 146A, 15.6.1990. EINECS is an inventory of substances that were deemed to be on the European Community market between 1 January 1971 and 18 September 1981. EINECS was drawn up by the European Commission in the application of Article 13 of Directive 67/548/EEC, as amended by Directive 79/831/EEC, and in accordance with the detailed provisions of Commission Decision 81/437/EEC. Substances listed in EINECS are considered phase-in substances under the REACH Regulation ...
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294546299 - EP 1076563 A1 2001-02-21 - DIPEPTIDE CASPASE INHIBITORS AND THE USE THEREOF - [origin: WO9947154A1] The present invention is directed to novel dipeptides thereof, represented by general Formula (I): where R1-R2 and AA are defined herein. The present invention relates to the discovery that compounds having Formula (I) are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.[origin: WO9947154A1] The present invention is directed to novel dipeptides thereof, represented by general Formula (I): where R1-R2 and AA are defined herein. The present invention relates to the discovery that compounds having Formula (I) are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or
Apoptotic cells release the nucleotides ATP and UTP to attract phagocytic cells, which in turn clear the apoptotic cells. Chekeni et al. found that carbenoxolone (CBX), which inhibits connexins (which form gap junctions) and pannexins (which form plasma membrane channels), and probenicid, which is thought to be more specific for pannexins, reduced ATP release from apoptotic Jurkat cells to a similar extent as the caspase inhibitor zVAD (which blocks the release of ATP from apoptotic cells). Small interfering RNAs (siRNAs) directed against pannexin 1 (PANX1) decreased the release of ATP and UTP from apoptotic Jurkat cells but did not prevent apoptosis. Supernatant from PANX1 siRNA-transfected apoptotic cells recruited fewer monocytes in an in vitro assay of cell migration and when placed in a subcutaneous air pouch in mice. In contrast, Jurkat cells stably overexpressing PANX1 released more ATP and UTP, and supernatants from these cells (after apoptosis had been induced) recruited more monocytes ...
In eukaryotic cells, there are 2 different forms of cell death: necrosis and apoptosis.19 Necrosis is considered to be a nonphysiological cell death. Necrosis is characterized as an uncoordinated collapse of cellular homeostasis, resulting in early damage of the plasma membrane and consequently the loss of the integrity of the cell. In contrast, apoptosis is a process of programmed cell death in which unnecessary cells are eliminated from multicellular organism. In apoptotic changes, condensation of the nucleus chromatin and fragmentation of the DNA are manifested. The cell shrinks as a result of cytoplasmic condensation, and organelles preserve their normal ultrastructure. The plasma membrane becomes ruffled and blebbed, which eventually separates the cell into a number of membrane-bound fragments of different sizes. The fragments are known as "apoptotic bodies."20 Besides its normal role in the development and maintenance of proliferating mature tissue, apoptosis is also involved in abnormal ...
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benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone
     Summary Report | CureHunterbenzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone Summary Report | CureHunter

benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone: a dipeptide caspase inhibitor with potent in vivo antiapoptotic ... Amino Acids, Peptides, and Proteins*Amino Acids: 10808*Amino Acid Chloromethyl Ketones*benzyloxycarbonyl-valyl-aspartic acid ... benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone. Subscribe to New Research on benzyloxycarbonyl-valyl-aspartic acid ... EP1013; MX1013; N-benzyloxycabonyl-Val Asp-fluoromethyl ketone; Z-VD-FMK; zVD-FMK ...
more infohttp://www.curehunter.com/public/keywordSummaryC484771-benzyloxycarbonyl-valyl-aspartic-acid-fluoromethyl-ketone.do

Caspase-3 activation occurs in various lymphocyte subse | Open-iCaspase-3 activation occurs in various lymphocyte subse | Open-i

Amino Acid Chloromethyl Ketones/pharmacology. *Caspase Inhibitors. *Cysteine Proteinase Inhibitors/pharmacology. *Humans ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2195712_JEM980433.f3b&req=4

Inhibition of apoptosis by Z-VAD-fmk in SMN-depleted S2 cells by Raju Ilangovan, William L. Marshall et al."Inhibition of apoptosis by Z-VAD-fmk in SMN-depleted S2 cells" by Raju Ilangovan, William L. Marshall et al.

Amino Acid Chloromethyl Ketones; Animals; Antibodies; Apoptosis; Caspases; Cell Line; Cyclic AMP Response Element-Binding ...
more infohttps://escholarship.umassmed.edu/oapubs/716/

phenylalanyl-phenylalanyl-arginine chloromethyl ketone - Semantic Scholarphenylalanyl-phenylalanyl-arginine chloromethyl ketone - Semantic Scholar

Post-translational isomerization of l-amino acids to d-amino acids is a subtle modification, not detectable by standard… (More) ... phenylalanyl-phenylalanyl-arginine chloromethyl ketone. Known as: FFRCK, Phe-Phe-Arg-CK, L-Phenylalaninamide, D-phenylalanyl-N ... Characterization of D-amino-acid-containing excitatory conotoxins and redefinition of the I-conotoxin superfamily. ... 1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway… (More ...
more infohttps://www.semanticscholar.org/topic/phenylalanyl-phenylalanyl-arginine-chloromethyl/3886432

emphysemaemphysema

Amino Acid Chloromethyl Ketones. 13. + +. 12. Receptors, Autocrine Motility Factor. 13. + +. 13. Xenon Isotopes. 12. + +. ...
more infohttps://lookfordiagnosis.com/results.php?symptoms=emphysema&lang=1&parent=%2F&mode=F&therapy_ap=1

zVAD-fmk does not totally abrogate FasL-triggered apopt | Open-izVAD-fmk does not totally abrogate FasL-triggered apopt | Open-i

Amino Acid Chloromethyl Ketones/pharmacology*. *Antigens, CD95/metabolism*. *Caspase 10/physiology*. *Cell Death/physiology* ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2964310_pone.0013638.g008&req=4

Patent US20050147572 - Cosmetic composition containing a protein and an enzyme inhibitor - Google PatentsuchePatent US20050147572 - Cosmetic composition containing a protein and an enzyme inhibitor - Google Patentsuche

N-alpha-p-tosyl-L-lysyl-chloromethyl-ketone and other amino acid analogs and trypsin-chimotrypsin inhibitors. ... N-alpha-p-tosyl-L-lysyl-chloromethyl-ketone and trypsin-chimotrypsin inhibitors. ... N-alpha-p-tosyl-L-lysyl-chloromethyl-ketone and trypsin-chimotrypsin inhibitors. ... N-alpha-p-tosyl-L-lysyl-chloromethyl-ketone and trypsin-chimotrypsin inhibitors. ...
more infohttps://www.google.ch/patents/US20050147572

Protease activation in apoptosis induced by MALProtease activation in apoptosis induced by MAL

Amino Acid Chloromethyl Ketones, Animals, Apoptosis, Caspase 3, Caspase 6, Caspases, Cell Extracts, Cysteine Proteinase ... Amino Acid Chloromethyl Ketones,Animals,Apoptosis,Caspase 3,Caspase 6,Caspases,Cell Extracts,Cysteine Proteinase Inhibitors, ...
more infohttps://lup.lub.lu.se/search/publication/5b8f99f5-08ae-4701-a87c-1b45581f2ba5

US5279937A - Use of macroglobulins to improve the signal-to-background ratio in affinity binding assays 
        - Google...US5279937A - Use of macroglobulins to improve the signal-to-background ratio in affinity binding assays - Google...

Preferred examples are chloromethyl ketone derivatives of various amino acids and peptides, typically of molecular weight less ... Ultimate on-line detection can then be achieved by proteolytic formation of amino acids, and their reaction with an amino acid ... 65-178, in B. Weinstein (Ed.), Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins, Vol. 4, Marcel Dekker, New ... optionally joined by a linker of one or more amino acids. If this approach is undertaken, the linker is preferably rich in ...
more infohttps://patents.google.com/patent/US5279937

Peptide and Amino Acid Abvbreiations and their MeaningsPeptide and Amino Acid Abvbreiations and their Meanings

Commonly used amino acid and peptide abbreviations and their meanings ... Chloromethyl ketone. CMV Cytomegalovirus. CNP C-type Natriuretic Peptide. Cpa. Cyclopropylalanine. Cpg. Cyclpentylglycine. ... Azido Amino Acids. • Beta-Amino Acids. • Beta-Homo Amino Acids. • BOC-Amino Acids. - Boc-D-Amino Acids. - Boc-L-Amino Acids. • ... Fmoc-Amino Acid Wang Resins. • Fmoc-Amino Acids. - Fmoc-D-Amino Acids. - Fmoc-L-Amino Acids. - Fmoc-Amino Acid OPfp. • Glyco- ...
more infohttps://www.peptide.com/abbreviations-their-meanings-i-231.html

Glossary of Medical Terms | Hepatitis CentralGlossary of Medical Terms | Hepatitis Central

... the result is 22 known amino acids, 8 are essential amino acids, the rest are non-essential. Amino Acid Chloromethyl Ketones. ... Amino Acids, Branched-Chain. Amino acids which have a branched carbon chain. Amino Acids, Cyclic. Class of amino acids ... Amino Acid Sequence. The arrangement of amino acids in a protein. Proteins can be made from 20 different kinds of amino acids, ... The non-essential amino acids are also essential for health, but can be synthesized in the body from the essential amino acids ...
more infohttp://www.hepatitiscentral.com/hcv/glossary/a/

NAVER Academic > Search...NAVER Academic > Search...

Amino Acid Chloromethyl Ketones, pharmacology, Antineoplastic Agents, Phytogenic, isolation & purification, therapeutic use, ...
more infohttps://academic.naver.com/search.naver?field=3&query=Cancer+Letters+256%EA%B6%8C+2%ED%98%B8

NAVER Academic > Search...NAVER Academic > Search...

Alkaloids, pharmacology, Amino Acid Chloromethyl Ketones, Animals, Apoptosis, drug effects, Caspase 1, Cell Nucleus, Cells, ... Acetylglucosamine, analogs & derivatives, pharmacology, Adenosine Triphosphate, Amino Acid Sequence, Base Sequence, Chaperonin ...
more infohttps://academic.naver.com/search.naver?field=3&query=BIOCHEMICAL+JOURNAL+314+%28+Pt+1%29%EA%B6%8C

Detect Serine Protease Activity with the FLISP FAM-Phe-CMK AssayDetect Serine Protease Activity with the FLISP FAM-Phe-CMK Assay

... which is linked to the target amino acid phenylalanine, and a chloromethyl ketone (CMK) reactive group, forming the fluorescent ... Home / Cell Viability Assays / Serine Protease / Target Amino Acid: Phenylalanine / FAM FLISP FFCK Serine Protease Assay. ...
more infohttps://immunochemistry.com/product/flisp-fam-phe-cmk-serine-protease-assay-kit/

Entry into the stationary phase is associated with a rapid loss of viability and an apoptotic-like phenotype in the...Entry into the stationary phase is associated with a rapid loss of viability and an apoptotic-like phenotype in the...

Amino Acid Chloromethyl Ketones/pharmacology. *Apoptosis/physiology*. *Aspergillus fumigatus/cytology. *Aspergillus fumigatus/ ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/12892635?dopt=Abstract

Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients.  - PubMed - NCBICaspase activation in retinas of diabetic and galactosemic mice and diabetic patients. - PubMed - NCBI

Amino Acid Chloromethyl Ketones. *Biomarkers. *Cysteine Proteinase Inhibitors. *benzyloxycarbonylvalyl-alanyl-aspartyl ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/11916941

JCI -
Volume 87, Issue 5JCI - Volume 87, Issue 5

The deduced amino acid sequence for the E1 alpha subunit of the patients cell was normal. An 11-bp deletion was identified in ... Heat-inactivation, diisopropylfluorophosphate, PMSF, and N-benzyloxycarbonylglycylleucylphenylalanyl-chloromethyl ketone ... The HLA-DQB1*0301 chain shares an identical seven amino acid sequence with DQB1*0302, *0602, and *0603 chains in the third ... indicated that apo B67 was a truncated species of apo B that contained approximately the amino-terminal 3,000-3,100 amino acids ...
more infohttps://www.jci.org/87/5

Tosyl phenylalanyl chloromethyl ketone - WikipediaTosyl phenylalanyl chloromethyl ketone - Wikipedia

The phenylalanine moiety is bound to the enzyme because of specificity for aromatic amino acid residues at the active site (as ... Tosyl phenylalanyl chloromethyl ketone (TPCK) is a protease inhibitor. Its structural formula is 1-chloro-3-tosylamido-4-phenyl ... The chloromethyl group reacts with the active site cysteine to form a covalent bond with the loss of the chlorine. TPCK is ...
more infohttps://en.wikipedia.org/wiki/Tosyl_phenylalanyl_chloromethyl_ketone

Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. - Oxford...Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. - Oxford...

Amino Acid Chloromethyl Ketones, Apoptosis, Autoantigens, Caspase 3, Caspases, Enzyme Inhibitors, Glycoproteins, Golgi ...
more infohttps://www.neuroscience.ox.ac.uk/publications/528882

Role of Transmembrane Domain and Cytoplasmic Tail Amino Acid Sequences of Influenza A Virus Neuraminidase in Raft Association...Role of Transmembrane Domain and Cytoplasmic Tail Amino Acid Sequences of Influenza A Virus Neuraminidase in Raft Association...

... in the presence of 0.5 μg of tosylsulfonyl phenylalanyl chloromethyl ketone (TPCK)-treated trypsin (Sigma Chemical Co., St. ... amino acids from NA sequences. Amino acids shown in boldface type are from TR sequences. Amino acids in lowercase type are due ... Numbers above amino acid sequences represent amino acid positions (indicated by ↓) of the WT NA peptide. ... Although the 6 amino acids (aa) in the CT of NA are extremely conserved among the influenza A viruses (7), little is known ...
more infohttps://jvi.asm.org/content/78/10/5258?ijkey=7a46196eebd4cfb9a8f1bd416a9d379431545562&keytype2=tf_ipsecsha

Nuclear Factor-κB Mediates Simultaneous Induction of Inducible Nitric-Oxide Synthase and Up-Regulation of the Cationic Amino...Nuclear Factor-κB Mediates Simultaneous Induction of Inducible Nitric-Oxide Synthase and Up-Regulation of the Cationic Amino...

The NF-κB inhibitors pyrrolidine dithiocarbamate andN α-p-tosyl-l-lysine chloromethyl ketone abrogated LPS- and interferon-γ- ... This correlated with an increased mRNA expression for iNOS and the cationic amino acid transporter CAT-2B (analyzed by reverse ... Factor-κB Mediates Simultaneous Induction of Inducible Nitric-Oxide Synthase and Up-Regulation of the Cationic Amino Acid ... Factor-κB Mediates Simultaneous Induction of Inducible Nitric-Oxide Synthase and Up-Regulation of the Cationic Amino Acid ...
more infohttp://molpharm.aspetjournals.org/content/58/6/1294

Amino acid substitutions in hemagglutinin of the 2009 pandemic influenza A(H1N1) viruses that might affect the viral...Amino acid substitutions in hemagglutinin of the 2009 pandemic influenza A(H1N1) viruses that might affect the viral...

An accumulation of amino acid substitutions in HA was observed in viruses derived from the late epidemic waves. Significantly ... supplemented with 2 μg/ml of L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin (Sigma, St. Louis, MO). ... Number of amino acids involved (position). Number of amino acid residues identical to A/CA/07/2009 (H1N1) (amino acid ... Amino acid sequences of HA protein, including the HA1 globular head (amino acid positions 42-275 which spanned the Sa, Sb, Ca, ...
more infohttps://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-7-951

4-Aminoethylpiperazinyl aryl ketones with 5-HT₁A/5-HT₇ selectivity. - Semantic Scholar4-Aminoethylpiperazinyl aryl ketones with 5-HT₁A/5-HT₇ selectivity. - Semantic Scholar

The 4-aminoethylpiperazinyl aryl ketones showed a wide spectrum of activity and selectivity for the 5-HT receptors depending on ... inhibitory activity as well as selectivity of the 4-aminoethylpiperazinyl aryl ketones against 5-HT(7)R and 5-HT(1A)R seemed to ... selectivity issue was tackled by a new series of 4-aminoethylpiperazinyl aryl ketones (1a-1l) specifically designed to ... the type of the hydrophobic groups attached at the aryl piperazinyl ketone scaffold. Docking study of the most active compounds ...
more infohttps://www.semanticscholar.org/paper/4-Aminoethylpiperazinyl-aryl-ketones-with-Kim-Lee/46f2ecd7ad5320e9629460671857648b647ddeb8

Rene Maehrs research topics | Profiles RNSRene Maehr's research topics | Profiles RNS

Amino Acid Chloromethyl Ketones. *Amino Acid Sequence. *Angelman Syndrome. *Animals. *Antigen Presentation ...
more infohttps://profiles.umassmed.edu/display/132067/Network/ResearchAreas
  • The HA protein, a type I transmembrane protein, is responsible for binding to the cell surface sialic acid (the receptor), eliciting neutralizing antibodies, and mediating virus entry into the cell by fusion of the viral membrane with the endosomal membrane ( 46 ). (asm.org)
  • Amino Acids" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
  • To investigate the role of amino acid sequences of the CT and TMD on the virus life cycle, we systematically mutagenized the entire CT and TMD of NA by converting two to five contiguous amino acids to alanine. (asm.org)
  • It has been shown previously that NA is not required for virus replication or budding except in the final step of releasing the virus particles from the cell surface sialic acid receptor as well as preventing aggregation among the progeny virus particles ( 29 ). (asm.org)
  • The HLA-DQB1*0301 chain shares an identical seven amino acid sequence with DQB1*0302, *0602, and *0603 chains in the third hypervariable region of the HLA-DQ molecule. (jci.org)
  • The well-known 5-HT(1A)/5-HT(7) selectivity issue was tackled by a new series of 4-aminoethylpiperazinyl aryl ketones (1a-1l) specifically designed to distinguish the two hydrophobic sites centered at the anchoring salt bridge. (semanticscholar.org)
  • Among the influenza A viruses, both the cytoplasmic tail (CT) and transmembrane domain (TMD) amino acid sequences of NA are highly conserved, yet their function(s) in virus biology remains unknown. (asm.org)
  • An accumulation of amino acid substitutions in HA was observed in viruses derived from the late epidemic waves. (biomedcentral.com)
  • The method comprises oral administration of ascorbic acid, a source of biologically available calcium, a precursor or stimulant of epinephrine or nor-epinephrine selected from tyrosine and phenylalanine, and an anti-inflammatory substance selected from anti-inflammatory sugars, amino sugars and biocompatible acid addition salts thereof, and anti-inflammatory amino acids. (patents.com)
  • These results show that although the sequences of NA CT and TMD per se are not absolutely essential for the virus life cycle, specific amino acid sequences play a critical role in providing structural stability, enzyme activity, and lipid raft association of NA. (asm.org)
  • The NF-κB inhibitors pyrrolidine dithiocarbamate and N α - p -tosyl- l -lysine chloromethyl ketone abrogated LPS- and interferon-γ-induced increase of nitrite accumulation and l -[ 3 H]arginine uptake as well as up-regulation of iNOS and CAT-2B mRNA. (aspetjournals.org)
  • A substitution of Asp-to-Gly at position 222 in the HA protein was prone to occur under positive selection pressures, and this single amino acid mutation could dramatically increase the virus replication ability in vitro and pathogenicity in vivo . (biomedcentral.com)