1-Deoxynojirimycin: An alpha-glucosidase inhibitor with antiviral action. Derivatives of deoxynojirimycin may have anti-HIV activity.alpha-Glucosidases: Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.GlucosamineIndolizinesMorus: A plant genus of the family MORACEAE that is widely planted for shade.Swainsonine: An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-.Mannosidases: Glycoside hydrolases that catalyze the hydrolysis of alpha or beta linked MANNOSE.alpha-Mannosidase: An enzyme that catalyzes the HYDROLYSIS of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. The enzyme plays a role in the processing of newly formed N-glycans and in degradation of mature GLYCOPROTEINS. There are multiple isoforms of alpha-mannosidase, each having its own specific cellular location and pH optimum. Defects in the lysosomal form of the enzyme results in a buildup of mannoside intermediate metabolites and the disease ALPHA-MANNOSIDOSIS.Oligosaccharides: Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.Imino Furanoses: Five-carbon furanose sugars in which the OXYGEN is replaced by a NITROGEN atom.Imino Pyranoses: Six-carbon pyranose sugars in which the OXYGEN is replaced by a NITROGEN atom.Glucan 1,4-alpha-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of polysaccharide chains with the release of beta-glucose. It is also able to hydrolyze 1,6-alpha-glucosidic bonds when the next bond in sequence is 1,4.Imino Sugars: Sugars in which the OXYGEN is replaced by a NITROGEN atom. This substitution prevents normal METABOLISM resulting in inhibition of GLYCOSIDASES and GLYCOSYLTRANSFERASES.Acarbose: An inhibitor of ALPHA-GLUCOSIDASES that retards the digestion and absorption of DIETARY CARBOHYDRATES in the SMALL INTESTINE.Sodium-Glucose Transport Proteins: Monosaccharide transport proteins that function as active symporters. They utilize SODIUM or HYDROGEN IONS to transport GLUCOSE across CELL MEMBRANES.Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase: A group of related enzymes responsible for the endohydrolysis of the di-N-acetylchitobiosyl unit in high-mannose-content glycopeptides and GLYCOPROTEINS.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Hexosaminidases: Enzymes that catalyze the hydrolysis of N-acylhexosamine residues in N-acylhexosamides. Hexosaminidases also act on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES.Mannose: A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed)Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Pituitary Hormones, Anterior: Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Structurally, they include polypeptide, protein, and glycoprotein molecules.Glucosyltransferases: Enzymes that catalyze the transfer of glucose from a nucleoside diphosphate glucose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.beta-Glucosidase: An exocellulase with specificity for a variety of beta-D-glycoside substrates. It catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of GLUCOSE.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Carbohydrate Sequence: The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.Glycoside HydrolasesKinetics: The rate dynamics in chemical or physical systems.Emulsions: Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.Lecithins: A complex mixture of PHOSPHOLIPIDS; GLYCOLIPIDS; and TRIGLYCERIDES; with substantial amounts of PHOSPHATIDYLCHOLINES; PHOSPHATIDYLETHANOLAMINES; and PHOSPHATIDYLINOSITOLS, which are sometimes loosely termed as 1,2-diacyl-3-phosphocholines. Lecithin is a component of the CELL MEMBRANE and commercially extracted from SOYBEANS and EGG YOLK. The emulsifying and surfactant properties are useful in FOOD ADDITIVES and for forming organogels (GELS).Fat Emulsions, Intravenous: Emulsions of fats or lipids used primarily in parenteral feeding.Monomethylhydrazine: Hydrazine substituted by one methyl group.Sulfonic Acids: Inorganic or organic oxy acids of sulfur which contain the RSO2(OH) radical.Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Naphthalenesulfonates: A class of organic compounds that contains a naphthalene moiety linked to a sulfonic acid salt or ester.Anilino Naphthalenesulfonates: A class of organic compounds which contain an anilino (phenylamino) group linked to a salt or ester of naphthalenesulfonic acid. They are frequently used as fluorescent dyes and sulfhydryl reagents.Colitis: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.Moraceae: The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.Plant Leaves: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed)Powders: Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed)Bombyx: A genus of silkworm MOTHS in the family Bombycidae of the order LEPIDOPTERA. The family contains a single species, Bombyx mori from the Greek for silkworm + mulberry tree (on which it feeds). A native of Asia, it is sometimes reared in this country. It has long been raised for its SILK and after centuries of domestication it probably does not exist in nature. It is used extensively in experimental GENETICS. (From Borror et al., An Introduction to the Study of Insects, 4th ed, p519)Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Medicine, Chinese Traditional: A system of traditional medicine which is based on the beliefs and practices of the Chinese culture.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Medicine, East Asian Traditional: Medical practice or discipline that is based on the knowledge, cultures, and beliefs of the people in EAST ASIA.Pinellia: A plant genus of the family ARACEAE that contains pinellian (an acidic polysaccharide). The plant is an ingredient of some traditional Asian medicinal mixtures including sho-saiko-to, saiko-keishi-to, and banxia houpu decoction.Cinnamomum aromaticum: A plant species of the genus CINNAMOMUM that contains CINNAMATES and has been used in traditional Chinese medicine (DRUGS, CHINESE HERBAL).Poria: A genus of basiodiomycetous fungi in the family Coriolaceae. Members are known for infesting wood.Glycogen Storage Disease Type II: An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Oligo-1,6-Glucosidase: An enzyme that catalyzes the endohydrolysis of 1,6-alpha-glucosidic linkages in isomaltose and dextrins produced from starch and glycogen by ALPHA-AMYLASES. EC 3.2.1.10.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

Trypanosoma cruzi calreticulin is a lectin that binds monoglucosylated oligosaccharides but not protein moieties of glycoproteins. (1/366)

Trypanosoma cruzi is a protozoan parasite that belongs to an early branch in evolution. Although it lacks several features of the pathway of protein N-glycosylation and oligosaccharide processing present in the endoplasmic reticulum of higher eukaryotes, it displays UDP-Glc:glycoprotein glucosyltransferase and glucosidase II activities. It is herewith reported that this protozoan also expresses a calreticulin-like molecule, the third component of the quality control of glycoprotein folding. No calnexin-encoding gene was detected. Recombinant T. cruzi calreticulin specifically recognized free monoglucosylated high-mannose-type oligosaccharides. Addition of anti-calreticulin serum to extracts obtained from cells pulse-chased with [35S]Met plus [35S]Cys immunoprecipitated two proteins that were identified as calreticulin and the lysosomal proteinase cruzipain (a major soluble glycoprotein). The latter but not the former protein disappeared from immunoprecipitates upon chasing cells. Contrary to what happens in mammalian cells, addition of the glucosidase II inhibitor 1-deoxynojirimycin promoted calreticulin-cruzipain interaction. This result is consistent with the known pathway of protein N-glycosylation and oligosaccharide processing occurring in T. cruzi. A treatment of the calreticulin-cruzipain complexes with endo-beta-N-acetylglucosaminidase H either before or after addition of anti-calreticulin serum completely disrupted calreticulin-cruzipain interaction. In addition, mature monoglucosylated but not unglucosylated cruzipain isolated from lysosomes was found to interact with recombinant calreticulin. It was concluded that the quality control of glycoprotein folding appeared early in evolution, and that T. cruzi calreticulin binds monoglucosylated oligosaccharides but not the protein moiety of cruzipain. Furthermore, evidence is presented indicating that glucosyltransferase glucosylated cruzipain at its last folding stages.  (+info)

Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. (2/366)

Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the beta-subunit of beta-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.  (+info)

Cellobiose transport by mixed ruminal bacteria from a Cow. (3/366)

The transport of cellobiose in mixed ruminal bacteria harvested from a holstein cow fed an Italian ryegrass hay was determined in the presence of nojirimycin-1-sulfate, which almost inhibited cellobiase activity. The kinetic parameters of cellobiose uptake were 14 microM for the Km and 10 nmol/min/mg of protein for the Vmax. Extracellular and cell-associated cellobiases were detected in the rumen, with both showing higher Vmax values and lower affinities than those determined for cellobiose transport. The proportion of cellobiose that was directly transported before it was extracellularly degraded into glucose increased as the cellobiose concentration decreased, reaching more than 20% at the actually observed levels of cellobiose in the rumen, which were less than 0.02 mM. The inhibitor experiment showed that cellobiose was incorporated into the cells mainly by the phosphoenolpyruvate phosphotransferase system and partially by an ATP-dependent and proton-motive-force-independent active transport system. This finding was also supported by determinations of phosphoenolpyruvate phosphotransferase-dependent NADH oxidation with cellobiose and the effects of artificial potentials on cellobiose transport. Cellobiose uptake was sensitive to a decrease in pH (especially below 6.0), and it was weakly but significantly inhibited in the presence of glucose.  (+info)

Molecular chaperones stimulate the functional expression of the cocaine-sensitive serotonin transporter. (4/366)

The serotonin transporter (SERT) is an N-glycosylated integral membrane protein that is predicted to contain 12 transmembrane regions. SERT is the major binding site in the brain for antidepressant drugs, and it also binds amphetamines and cocaine. The ability of various molecular chaperones to interact with a tagged version of SERT (Myc-SERT) was investigated using the baculovirus expression system. Overexpression of Myc-SERT using the baculovirus system led to substantial quantities of inactive transporter, together with small amounts of fully active and, therefore, correctly folded molecules. The high levels of inactive Myc-SERT probably arose because folding was rate-limiting due, perhaps, to insufficient molecular chaperones. Therefore, Myc-SERT was co-expressed with the endoplasmic reticulum (ER) molecular chaperones calnexin, calreticulin and immunoglobulin heavy chain binding protein (BiP), and the foldase, ERp57. The expression of functional Myc-SERT, as determined by an inhibitor binding assay, was enhanced nearly 3-fold by co-expressing calnexin, and to a lesser degree on co-expression of calreticulin and BiP. Co-expression of ERp57 did not increase the functional expression of Myc-SERT. A physical interaction between Myc-SERT-calnexin and Myc-SERT-calreticulin was demonstrated by co-immunoprecipitation. These associations were inhibited in vivo by deoxynojirimycin, an inhibitor of N-glycan precusor trimming that is known to prevent the calnexin/calreticulin-N-glycan interaction. Functional expression of the unglycosylated SERT mutant, SERT-QQ, was also increased on co-expression of calnexin, suggesting that the interaction between calnexin and SERT is not entirely dictated by the N-glycan. SERT is the first member of the neurotransmitter transporter family whose folding has been shown to be assisted by the molecular chaperones calnexin, calreticulin, and BiP.  (+info)

Temporal association of the N- and O-linked glycosylation events and their implication in the polarized sorting of intestinal brush border sucrase-isomaltase, aminopeptidase N, and dipeptidyl peptidase IV. (5/366)

The temporal association between O-glycosylation and processing of N-linked glycans in the Golgi apparatus as well as the implication of these events in the polarized sorting of three brush border proteins has been the subject of the current investigation. O-Glycosylation of pro-sucrase-isomaltase (pro-SI), aminopeptidase N (ApN), and dipeptidyl peptidase IV (DPPIV) is drastically reduced when processing of the mannose-rich N-linked glycans is blocked by deoxymannojirimycin, an inhibitor of the Golgi-located mannosidase I. By contrast, O-glycosylation is not affected in the presence of swainsonine, an inhibitor of Golgi mannosidase II. The results indicate that removal of the outermost mannose residues by mannosidase I from the mannose-rich N-linked glycans is required before O-glycosylation can ensue. On the other hand, subsequent mannose residues in the core chain impose no sterical constraints on the progression of O-glycosylation. Reduction or modification of N- and O-glycosylation do not affect the transport of pro-SI, ApN, or DPPIV to the cell surface per se. However, the polarized sorting of two of these proteins, pro-SI and DPPIV, to the apical membrane is substantially altered when O-glycans are not completely processed, while the sorting of ApN is not affected. The processing of N-linked glycans, on the other hand, has no influence on sorting of all three proteins. The results indicate that O-linked carbohydrates are at least a part of the sorting mechanism of pro-SI and DPPIV. The sorting of ApN implicates neither O-linked nor N-linked glycans and is driven most likely by carbohydrate-independent mechanisms.  (+info)

VIP36 localisation to the early secretory pathway. (6/366)

VIP36, an integral membrane protein previously isolated from epithelial MDCK cells, is an intracellular lectin of the secretory pathway. Overexpressed VIP36 had been localised to the Golgi complex, plasma membrane and endocytic structures suggesting post-Golgi trafficking of this molecule (Fiedler et al., 1994). Here we provide evidence that endogenous VIP36 is localised to the Golgi apparatus and the early secretory pathway of MDCK and Vero cells and propose that retention is easily saturated. High resolution confocal microscopy shows partial overlap of VIP36 with Golgi marker proteins. Punctate cytoplasmic structures colocalise with coatomer and ERGIC-53, labeling ER-Golgi intermediate membrane structures. Cycling of VIP36 is suggested by colocalisation with anterograde cargo trapped in pre-Golgi structures and modification of its N-linked carbohydrate by glycosylation enzymes of medial Golgi cisternae. Furthermore, after brefeldin A treatment VIP36 is segregated from resident Golgi proteins and codistributes with ER-Golgi recycling proteins.  (+info)

Effects of N-butyldeoxynojirimycin and the Lec3.2.8.1 mutant phenotype on N-glycan processing in Chinese hamster ovary cells: application to glycoprotein crystallization. (7/366)

Heterologous gene expression in either (1) the glycosylation-defective, mutant Chinese hamster ovary cell line, Lec3.2.8.1, or (2) the presence of the alpha-glucosidase inhibitor, N-butyldeoxynojirimycin facilitates the trimming of N-linked glycans of glycoproteins to single N-acetylglucosamine (GlcNAc) residues with endoglycosidase H (endo H). Both approaches are somewhat inefficient, however, with as little as 12% of the total protein being rendered fully endo H-sensitive under these conditions. It is shown here that the combined effects of these approaches on the restriction of oligosaccharide processing are essentially additive, thereby allowing the production of glycoproteins that are essentially completely endo H-sensitive. The preparation of a soluble chimeric form of CD58, the ligand of the human T-cell surface recognition molecule CD2, illustrates the usefulness of the combined approach when expression levels are low or the deglycosylated protein is unstable at low pH. The endo H-treated chimera produced crystals of space group P3(1)21 or P3(2)21, and unit cell dimensions a = b = 116.4 A, c = 51.4 A alpha = beta = 90 degrees , gamma = 120 degrees , that diffract to a maximum resolution of 1.8 A.  (+info)

High-mannose type oligosaccharide-dependent apoptosis in U937 cells induced by pradimicin, a mannose-binding antibiotic. (8/366)

Cell surface oligosaccharides play a role in a variety of biological events such as cell adhesion and signal transduction. We have shown that BMY-28864, a semi-synthetic analog of pradimicin, induced apoptosis of U937 cells which had been incubated with 1-deoxymannojirimycin, an inhibitor of mannosidase I. BMY-28864 was not cytotoxic to the cells which had been cultivated with other glycosidase inhibitors such as castanospermine and swainsonine. We thus propose that BMY-28864 induces apoptosis by acting on a specific mannose-rich oligosaccharide, presumably (Man)9(GlcNAc)2+.  (+info)

How is Nojirimycin 6-Phosphate abbreviated? N6P stands for Nojirimycin 6-Phosphate. N6P is defined as Nojirimycin 6-Phosphate very rarely.
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An edible fat-continuous emulsion comprising 1-deoxynojirimycin (DNJ) and lecithin, wherein the lecithin comprises phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE) wherein the weight ratio (PC+PI)/PE is at least 2.5. A method to prepare such and the use of such emulsion.
Miglustat (OGT 918, N-butyl-deoxynojirimycin) is a drug developed by Oxford GlycoSciences and marketed by Actelion and is used primarily to treat type I Gaucher disease (GD1). It is marketed under the trade name Zavesca. Miglustat is used to treat adults with mild-to-moderate type I Gaucher disease for whom enzyme replacement therapy is unsuitable. It was approved in Europe in 2002 and by the US FDA in 2003. Miglustat is the first treatment to be approved for treating progressive neurological complications in people with Niemann-Pick disease, type C (NPC); it has been approved in Europe in 2009, Canada in 2010, and Japan in 2012, but not in the US where the FDA declined to approve it in 2010 and called for more data. Miglustat is contraindicated for people with neurological conditions, kidney problems, women who are pregnant, and men and women planning to conceive a child. Serious side effects include pain, burning, numbness or tingling in the hands, arms, legs, or feet; shaking hands that ...
Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site. Our design of α-1-C-heptyl-1,4-dideoxy-1,4-imino-l-arabinitol (LAB) produced a potent inhibitor of the GAA, with an IC50 value of 0.44 µM. It displayed a remarkable ...
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Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytoplasm and degraded by the proteasome. Processing intermediates of N-linked oligosaccharides on incompletely folded glycoproteins have an important role in their folding/refolding, and also in their targeting to proteolytic degradation. In Saccharomyces cerevisiae, we have identified a gene coding for a non-essential protein that is homologous to mannosidase I (HTM1) and that is required for degradation of glycoproteins. Deletion of the HTM1 gene does not affect oligosaccharide trimming. However, deletion of HTM1 does reduce the rate of degradation of the mutant glycoproteins such as carboxypeptidase Y, ABC-transporter Pdr5-26p and oligosaccharyltransferase subunit Stt3-7p, but not of mutant Sec61-2p, a non-glycoprotein. Our results indicate that although Htm1p is not involved in processing of N-linked oligosaccharides, it is required for their proteolytic degradation. We propose that this mannosidase ...
1NOK: Ternary complex crystal structures of glycogen phosphorylase with the transition state analogue nojirimycin tetrazole and phosphate in the T and R states.
Using N-butyl-deoxynojirimycin (NB-DNJ), a competitive inhibitor of the ER alpha-glucosidases, we have recently addressed the impact of this inhibition on both assembly and infectivity of the virions released from infected hepatoma cells. Southern and Western blotting analysis of HBV secreted from drug-treated cells showed that the envelope glycoprotein composition was severely altered, resulting in a significant reduction of HBV infectivity (80% compared to controls ...
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Miglitol is a medicine available in a number of countries worldwide. A list of US medications equivalent to Miglitol is available on the Drugs.com website.
1NOI: Ternary complex crystal structures of glycogen phosphorylase with the transition state analogue nojirimycin tetrazole and phosphate in the T and R states.
RBF/DnJ, also known as POSF, is an inbred strain of mouse model that is especially useful for antibody production. Learn more about their characteristics
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Shaarey Tphiloh Finance Committee statement A statement signed by members of the Finance Committee of Shaarey Tphiloh shows $330.25 in receipts from July 25, 1902 to Oct. 19, 1902. The group was raising money to build an Orthodox synagogue in Portland. It was built on Newbury Street and opened in 1 ( Portland ...
Shaarey Tphiloh Finance Committee statement A statement signed by members of the Finance Committee of Shaarey Tphiloh shows $330.25 in receipts from July 25, 1902 to Oct. 19, 1902. The group was raising money to build an Orthodox synagogue in Portland. It was built on Newbury Street and opened in 1 ( 1902 ...
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[email protected] Supervisors: Hans Aerts & Andries Kalsbeek. Iminosugars, carbohydrate analogues with the ring oxygen replaced by nitrogen, have attracted interest from life science researchers for decades due to their remarkable chemical, biological and pharmaceutical properties. The action of natural iminosugars stems from their capacity to interfere with glycoconjugate processing activities and it is for this reason that iminosugars are widely regarded as ideal starting point for the development of new therapeutic agents. Some iminosugars are currently successfully applied to treat Gaucher disease and diabetes mellitus type 2.. The lypophilic iminosugar AMP-DMN or MZ21 (adamantine methyloxypentyl-deoxynojirimycin) has proven to be one of the most efficient molecules in correcting the hyperglycemia and the metabolic syndrome present in obesity and diabetes type 2 animal models, as compared to other iminosugar compounds. It is also the only compound capable of decreasing food intake ...
Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gauchers disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is
We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of ′hit′ compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21h, 21k, 21n, 21 t, and 21 x with improved activities (IC50=12-30 mm) and low Jurkat cytotoxicities (IC50>100 mm). These new compounds also inhibited the secretion of IFN-gamma and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with ...
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Optimal glycemic control in type 2 diabetes may require multiple forms of therapy, and an increasing number of hypoglycemic agents are now available. The study by Holman and colleagues describes the glucose-lowering properties of acarbose, an α-glucosidase inhibitor that is used as an adjunct to preexisting therapy. This study confirms earlier reports of the efficacy of acarbose (1). Based on its mechanism of action, which is the delay of carbohydrate absorption, acarbose should predominantly affect postprandial hyperglycemia. This is supported by the current data showing that acarbose had no effect on FPG level but was associated with lowered HbA1c levels at 3 years. Although increased gut carbohydrate absorption has not traditionally been seen as a contributor to postprandial hyperglycemia, recent data suggest that splanchnic glucose uptake may be altered (2). Delayed entry of glucose from the gut by α-glucosidase inhibition may alleviate these altered splanchnic responses. The major problem ...
Conclusions: Type 2 Diabetes forms a significant share of the Diabetic load in India where cereals in the form of carbohydrates form the staple diet of most Indians. Thus α glucosidase inhibitors like Miglitol and acarbose are sure to play an important role as an add on therapy when first line drugs like sulphonylurea and biguanides fail to control the hyperglycaemia and they have minimum adverse effects, with more or less similar efficacy with Miglitol being better than Acarbose... Key words: Type 2 Diabetes Mellitus, Hyperglycaemia, PPBS, HbA1c, Miglitol, Acarbose ...
As Professor Zitzmann explains, the cycle has become a target for anti-virals: We think that viral proteins may have to go round the cycle multiple times before they are free to leave, which is much less likely to happen for normal cellular proteins. We know this is the case for HIV gp120. Our idea is to prevent viral proteins from entering the cycle by acting at α-glucosidase I and α-glucosidase II.. Their work is currently focused on using glycomimetics called iminosugars to do this. As competitive inhibitors of α-glucosidases, these are a promising class of antivirals because they target a broad range of viruses without the risk of losing efficacy because of mutations in the viral genome. Iminosugars are currently in phase I and phase II clinical trials for dengue fever. Because iminosugars are same-site binding inhibitors, they have off-target effects and also affect intestinal α-glucosidases, which are very similar.. Whilst the focus has been on improving the efficacy of iminosugars, ...
We investigated the influence of a glycosylphosphatidylinositol (GPI) anchor on the ectodomain of the influenza hemagglutinin (HA) by replacing the wild type (wt) transmembrane and cytoplasmic domains with a GPI lipid anchor. GPI-anchored HA (GPI-HA) was transported to the cell surface with equal efficiency and at the same rate as wt-HA. Like wt-HA, cell surface GPI-HA, and its ectodomain released with the enzyme PI-phospholipase C (PI-PLC), were 9S trimers. Compared to wt-HA, the GPI-HA ectodomain underwent additional terminal oligosaccharide modifications; some of these occurred near the receptor binding pocket and completely inhibited the ability of GPI-HA to bind erythrocytes. Growth of GPI-HA-expressing cells in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) abrogated the differences in carbohydrate modification and restored the ability of GPI-HA to bind erythrocytes. The ectodomain of GPI-HA produced from cells grown in the presence or absence of dMM underwent ...
Although miglustat has been approved as a treatment for mild to moderate type 1 Gaucher disease in patients who are unsuitable for enzyme replacement therapy (ERT), more data are required to establish the long term efficacy, safety and tolerability of miglustat in maintaining diseases stability after a switch from ERT ...
Figure 10DNJ did not show GAA translocation activity in Pompe fibroblasts (left panels are untreated and right panels are DNJ 20 μM) ...
Mannonojiritetrazole (7), a novel mannosidase inhibitor, has been synthesized in six steps from 2,3,4,6-tetra-O-benzyl-D-mannose oxime. The structure of 7 has been established by X-ray analysis. The solid state conformation of 7 is H-6(7) (=H-4(3), numbering based on carbohydrate nomenclature), and the conformation in CD3OD is close to S-7 (sofa; = S-3, numbering based upon carbohydrate nomenclature), while the conformation of the previously synthesized analogue with the gluco configuration (6) is H-6(7), both in the solid state and in solution in D2O or CD3OD. Both 6 and 7 have been tested as inhibitors of each of a series of five alpha- and beta-glucosidases and -mannosidases as well as of a beta-galactosidase, and inhibition constants have been determined. A good correlation (p = 0.9) was found between log K-i for each inhibitor-enzyme pair and log (V-m/K-m) for the corresponding substrate-enzyme pair, thereby providing the first such proof for any glycosidase inhibitor being a transition ...
Miglustat was well be tolerated and appears to be an effective agent in the treatment characteristic of typhoid heaviness in throngs the limbs. The effectiveness of preparation to be used objects with care in treatment of the common dizziness has been evaluated in a group of university education students employing a blind l
This study compared the efficacy and tolerability of miglitol and mitiglinide, alone versus in combination, in Japanese patients with type 2 diabetes mellitus.
The IUPHAR/BPS Guide to Pharmacology. miglitol ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
Mignar 50 mg Tablet is the best cure for Type 2 diabetes. Know about Miglitol Reviews, Dosage, Price and Precautions. Buy Generic Glyset FOR $0.27/Tablet at USA visit now.
GLYSET (Miglitol) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
DMM's signature and nost-popular clean nose wiregate. The DMM Chimera quickdraw strikes the perfect balance between weight and practicality.
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... (AGIs) are a class of drugs used to treat type 2 diabetes. The key benefit of AGIs is that they do not cause hypoglycemia (low blood sugar) or weight gain and are taken orally. These drugs help lower blood sugar levels in the body by blocking the breakdown of starchy foods like bread and potatoes in the intestine and thus delaying the absorption of carbohydrates, according to the American Diabetes Association They also slow down the breakdown of some sugars, like table sugar. Because they work to slow digestion, AGIs are taken at the start of a meal. The alpha-glucosidase inhibitors available today (with brand names in parenthesis) are: acarbose (Precose) miglitol (Glyset) An ADA published article states that
Most subtypes of CDG are classified as disorders of N-glycosylation, which involves carbohydrates called N-linked oligosaccharides. These oligosaccharides are created in a specific order to create specific sugar trees, which are then attached to proteins on various cells. Disorders of N-glycosylation are due to an enzyme deficiency or other malfunction somewhere along the N-glycosylation pathway.. As long as the defect is not identified, disorders of N-glycosylation are subdivided into defects of oligosaccharide assembly and transfer (CDG-Ix) and defects in oligosaccharide trimming and processing that occur after they are bound to proteins (CDG-IIx). As soon as the defect in an individual patient is clarified, a CDG name is given according to the current nomenclature.. Disorders of N-glycosylation include:. PMM2-CDG - This disorder is the most common type of CDG. More than 700 individuals have been identified. The disorder can be broken down into three stages: infantile multisystem, ...
Four glycoproteins of apparent molecular weights 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) are detectable in human immunodeficiency virus type 2 (HIV-2) infected cells. The gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. The gp300, which is a dimeric form of gp140, the precursor of HIV-2 envelope glycoprotein, is probably formed by a pH dependent fusion in the endoplasmic reticulum. Such a doublet is also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 does not form a dimer during its processing. Experiments carried out with various inhibitors of oligosaccharide trimming enzymes suggest that transient dimerization of the glycoprotein precursor is required for its efficient transport to the Golgi apparatus and for its processing. The gp300 is useful for detecting antibodies to
Alpha-glucosidase inhibitors work by ambitious and reversible inhibition of those intestinal enzymes. They diminish the digestion of carbohydrates and delay glucose absorption. This happens in a smaller and moderate rise in blood glucose levels following meals, and efficiently throughout the day.. AGIs have exhibited in reducing post-meal blood sugars and therefore helping to lower HbA1c, especially while used in combination with other diabetes drugs.. ...
Alpha-glucosidase inhibitors, a class of drugs also known as starch blockers, function by slowing the absorption of certain carbohydrates in the gastrointestinal tract.
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We used eight independent data sources to maximise complete ascertainment of cases of diabetes.. Diabetes prescriptions database generated by the Medicines Monitoring Unit-This unit, which is a university based organisation supported by the Medicines Control Agency, has been described in detail elsewhere.8 9 Briefly, it has devised a method of capturing person specific dispensing for the whole of Tayside and, since January 1993, has recorded over 10 million prescription items specified by community health number. Of these items, we identified all prescriptions for antidiabetic drugs (insulin, sulphonylureas, biguanides, and α-glucosidase inhibitors) and for diagnostic and monitoring devices for diabetes (such as test strips and meters).. Hospital diabetes clinics-We integrated four databases: those of diabetes clinics from Ninewells Hospital, Dundee; Stracathro Hospital, Brechin; and Perth Royal Infirmary as well that of a young adult and paediatric clinic at Ninewells Hospital. These sources ...
Q1. Potency of action of a) Miglitol is six times higher than that of acarbose b) Acarbose is more than that of miglitol c) Miglitol and acarbose is equa
Increased understanding of the role of protein- and lipid-linked carbohydrates in a wide range of biological processes has led to interest in drugs that target the enzymes involved in glycosylation. But given the importance of carbohydrates in fundamental cellular processes such as protein folding, therapeutic strategies that modulate, rather than ablate, the activity of enzymes involved in glycosylation are likely to be a necessity. Two such approaches that use imino sugars to affect glycosylation enzymes now show considerable promise in the treatment of viral infections, such as hepatitis B, and glucosphingolipid storage disorders, such as Gaucher disease.
Response to study treatment on neuropathic pain defined as a reduction from baseline to Month 6 of at least 30% in the modified Brief Pain Inventory-Short Form 3 (BPI-SF3) score of neuropathic pain at its worst in the last 24 hours ...
Background: We examined the part of socio-economic status (SES) and marital status in premature mortality among working-age Russian males. mortality for alcohol-related causes. Summary: While dangerous drinking is known to be a leading cause of premature mortality among working-age Russian males, it is unwise to ignore additional factors. Given the considerable interpersonal and economic buy […]. Read More ». ...
This trial would have investigated the efficacy and tolerability of miglustat [Zavesca; Actelion Pharmaceuticals] in patients with cystic fibrosis that were
In this easy-to-follow guide, youll discover how to trim buds, the best bud-trimming tools, secrets to trimming buds wet or dry, and much more.
... produces deoxynojirimycin, deoxymannonojirimycin and hydroxystreptomycin. So, NW; Rho, JY; Lee, SY; ... "The biosynthesis of deoxynojirimycin and deoxymannonojirimycin in Streptomyces subrutilus". Journal of the Chemical Society, ... 194 (1): 93-8. doi:10.1016/s0378-1097(00)00514-0. PMID 11150672. Nemr, El Sayed H. El Ashry, Ahmed El (2007). Synthesis of ... ISBN 1-4051-4479-3. al.], Senior reporter, R.J. Ferrier ; reporters, R. Blattner-- [et (1993). Carbohydrate chemistry. a review ...
187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Murphy CI, Lennick M, Lehar SM, Beltz GA, Young E (Oct 1990 ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Usuki F, Ishiura S, Nonaka I, Sugita H (Apr 1988). "alpha- ... 181 (1): 180-92. doi:10.1016/0042-6822(91)90483-R. PMID 1704656. Dedera DA, Gu RL, Ratner L (Mar 1992). "Role of asparagine- ... 1 (1): 17-23. doi:10.1093/glycob/1.1.17. PMID 2136376. Land A, Braakman I (Aug 2001). "Folding of the human immunodeficiency ...
ISBN 978-1-4051-1922-1. Baechle D, Flad T, Cansier A, Steffen H, Schittek B, Tolson J, Herrmann T, Dihazi H, Beck A, Mueller GA ... 44 (1): 73-80. doi:10.1007/s00726-011-1089-6. PMID 21960143. Devosse T, Dutoit R, Migeotte I, De Nadai P, Imbault V, Communi D ... 9 (1): 1-9. doi:10.1089/dna.1990.9.1. PMID 2180427. Capony F, Rougeot C, Montcourrier P, Cavailles V, Salazar G, Rochefort H ( ... 46 (1): 23-38. doi:10.2478/v10042-008-0003-x. PMID 18296260. Briozzo P, Morisset M, Capony F, Rougeot C, Rochefort H (July 1988 ...
122 (1): 39-51. doi:10.1083/jcb.122.1.39. PMC 2119607 . PMID 8314846. Misago M, Liao YF, Kudo S, Eto S, Mattei MG, Moremen KW, ... 67 (1): 150-60. PMC 237347 . PMID 8093218. Yeh JC, Seals JR, Murphy CI, van Halbeek H, Cummings RD (Oct 1993). "Site-specific N ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (Dec 1988). "Role of ... 187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Moremen KW, Touster O, Robbins PW (Sep 1991). "Novel ...
181 (1): 180-92. doi:10.1016/0042-6822(91)90483-R. PMID 1704656. Dedera DA, Gu RL, Ratner L (1992). "Role of asparagine-linked ... 187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Murphy CI, Lennick M, Lehar SM, Beltz GA, Young E (1991). " ... 1 (1): 17-23. doi:10.1093/glycob/1.1.17. PMID 2136376. Land A, Braakman I (2001). "Folding of the human immunodeficiency virus ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ...
1 (1): 17-23. doi:10.1093/glycob/1.1.17. PMID 2136376. Reuser AJ, Kroos MA, Hermans MM, et al. (1995). "Glycogenosis type II ( ... 181 (1): 180-92. doi:10.1016/0042-6822(91)90483-R. PMID 1704656. Dedera DA, Gu RL, Ratner L (1992). "Role of asparagine-linked ... 187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Hermans MM, Kroos MA, van Beeumen J, et al. (1991). "Human ... Lysosomal alpha-glucosidase, also called α-1,4-glucosidase and acid maltase, is an enzyme (EC 3.2.1.20) that in humans is ...
1-deoxynojirimycin or duvoglustat 1-deoxygalactonojirimycin or migalastat, a drug for the treatment of Fabry disease Inouye, S ...
181 (1): 180-92. doi:10.1016/0042-6822(91)90483-R. PMID 1704656. Dedera DA, Gu RL, Ratner L (1992). "Role of asparagine-linked ... 1 (1): 17-23. doi:10.1093/glycob/1.1.17. PMID 2136376. Land A, Braakman I (2001). "Folding of the human immunodeficiency virus ... 187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Murphy CI, Lennick M, Lehar SM, et al. (1991). "Temporal ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ...
93 (1): 35-41. doi:10.1007/BF00218910. PMID 7505766. Venter JC, Adams MD, Myers EW, et al. (2001). "The sequence of the human ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Oh JH, Yang JO, Hahn Y, et al. (2005). "Transcriptome analysis of human ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The ... 16 (1): 55-65. doi:10.1101/gr.4039406. PMC 1356129 . PMID 16344560. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997 ...
Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase is an enzyme that in humans is encoded by the MGAT2 gene ... 67 (1): 150-60. PMC 237347 . PMID 8093218. Yeh JC, Seals JR, Murphy CI, et al. (1993). "Site-specific N-glycosylation and ... 406 (1-2): 191-5. doi:10.1016/S0014-5793(97)00273-1. PMID 9109416. GeneReviews/NCBI/NIH/UW entry on Congenital Disorders of ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ...
6 (1): 63-70. doi:10.1093/dnares/6.1.63. PMID 10231032. Park C, Meng L, Stanton LH, Collins RE, Mast SW, Yi X, Strachan H, ... 67 (1): 150-60. PMC 237347 . PMID 8093218. Yeh JC, Seals JR, Murphy CI, et al. (1993). "Site-specific N-glycosylation and ... 406 (1-2): 191-5. doi:10.1016/S0014-5793(97)00273-1. PMID 9109416. Hiramoto S, Tamba M, Kiuchi S, et al. (1998). "Stage- ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ...
67 (1): 150-60. PMC 237347 . PMID 8093218. Yeh JC, Seals JR, Murphy CI, et al. (1993). "Site-specific N-glycosylation and ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ... 187 (1): 377-82. doi:10.1016/0042-6822(92)90331-I. PMID 1736542. Kalyanaraman VS, Rodriguez V, Veronese F, et al. (1990). " ... 406 (1-2): 191-5. doi:10.1016/S0014-5793(97)00273-1. PMID 9109416. Tremblay LO, Campbell Dyke N, Herscovics A (1998). " ...
Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA is an enzyme that in humans is encoded by the MAN1A1 gene. This gene encodes ... 67 (1): 150-60. PMC 237347 . PMID 8093218. Yeh JC, Seals JR, Murphy CI, et al. (1993). "Site-specific N-glycosylation and ... 406 (1-2): 191-5. doi:10.1016/S0014-5793(97)00273-1. PMID 9109416. Bieberich E, Treml K, Völker C, et al. (1997). "Man9- ... 141 (1): 33-8. doi:10.1016/S0006-291X(86)80330-8. PMID 3099781. Montefiori DC, Robinson WE, Mitchell WM (1988). "Role of ...
Depending on the mutation, the EC50 is between 0.8 µM and over 1 mM in cellular models. The enzyme alpha-galactosidase A (α- ... Migalastat is used in form of the hydrochloride, which is a white crystalline solid and is soluble in water (≥1 mg/mL). The ... 1 April 2016. "Public summary of opinion on orphan designation". European Medicines Agency. 29 April 2014. Clinical trial ... The most common side effect in clinical trials was headache (in about 10% of patients). Less common side effects (between 1 and ...
Retrieved 1 March 2012. Wu XQ, Xu H, Yue H, Liu KQ, Wang XY (December 2009). "Inhibition kinetics and the aggregation of alpha- ... Retrieved 1 March 2012. Yoshimizu, M.; Tajima, Y; Matsuzawa, F; Aikawa, S; Iwamoto, K; Kobayashi, T; Edmunds, T; Fujishima, K; ... 306 (1): 188-94. doi:10.1006/abbi.1993.1499. PMID 8215402. Tadera K, Minami Y, Takamatsu K, Matsuoka T (April 2006). " ... It was shown that 1-deoxynojirimycin (DNJ) would bind the strongest of the sugars tested and blocked the active site of the ...
Nitrogen-containing, 'sugar-shaped' heterocycles have been found in nature, including deoxynojirimycin, swainsonine, australine ... 3 (1): 26-44. doi:10.2174/22115501113026660041. Fleming, Derek; Rumbaugh, Kendra P. (2017-04-01). "Approaches to Dispersing ... Glycoside hydrolases are classified into EC 3.2.1 as enzymes catalyzing the hydrolysis of O- or S-glycosides. Glycoside ... 2006, 1, 294-298. Naumoff, D.G. (2011). "Hierarchical classification of glycoside hydrolases". Biochemistry (Moscow). 76 (6): ...
The 1-deoxy analogs of iminosugars are C-glycosides, with the nitrogen as part of an ordinary amine linkage. Their piperidine, ... The first iminosugar to be isolated from a natural source, 1-deoxynojirimycin (DNJ), found in Mulberry, was reported in 1976, ... In terms of biochemical activity for medicinal applications, DNJ and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, another early ...
2-ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- MeSH D03.438.834.775 --- sparteine MeSH D03.438.834.850 --- ... 5-dihydro-1-(3-(trifluoromethyl)phenyl)-1h-pyrazol-3-amine MeSH D03.383.129.539.200 --- epirizole MeSH D03.383.129.539.487 --- ... 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, methyl ester MeSH D03.383.725.547.950 --- xanthinol niacinate ... 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, methyl ester MeSH D03.383.725.210 --- dimethindene MeSH ...
Deoxynojirimycin. Chaluntorn Vichasilp; et al. (2012). "Development of high 1-deoxynojirimycin (DNJ) content mulberry tea and ... 1-Deoxynojirimycin (DNJ), also called duvoglustat or moranolin, is an alpha-glucosidase inhibitor, most commonly found in ... "Production of the α-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species". Food chemistry. 138 (1): 516-23. doi: ... Nojirimycin 1-Deoxygalactonojirimycin, a stereoisomer of 1-deoxynojirimycin KEGG: ...
... (OGT 918, N-butyl-deoxynojirimycin) is a drug developed by Oxford GlycoSciences and marketed by Actelion and is used ... Yukhananov, Anna (1 May 2012). "U.S. FDA approves Pfizer/Protalix drug for Gaucher". Chicago Tribune. Reuters. Retrieved 2 May ... European Medicines Agency 1 April 2003 Scientific discussion related to approval of Zavesca. Clinicaltrials.gov ... Zavesca approved -- first oral treatment option for type 1 Gaucher disease UK Medicines Information. New Drugs Online Report ...
Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell ... 318 (1-2): 133-7. doi:10.1016/S0009-8981(02)00002-5. PMID 11880123. Kuliev A, Rechitsky S, Laziuk K, Verlinsky O, Tur-Kaspa I, ... 3 (1): 139-145. doi:10.1093/hmg/3.1.139. PMID 8162015. "From a parents perspective: Parents view of Sandhoff". sandhoffdisease. ... 107 (1): 12-17. doi:10.1007/s004390050003. PMID 10982028. Cantor RM, Kaback MM (1985). "Sandhoff disease (SHD) heterozygote ...
Deoxynojirimycin. Chaluntorn Vichasilp; et al. (2012). "Development of high 1-deoxynojirimycin (DNJ) content mulberry tea and ... 1-Deoxynojirimycin (DNJ), also called duvoglustat or moranolin, is an alpha-glucosidase inhibitor, most commonly found in ... "Production of the α-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species". Food chemistry. 138 (1): 516-23. doi: ... Nojirimycin 1-Deoxygalactonojirimycin, a stereoisomer of 1-deoxynojirimycin KEGG: ...
We also Provide Trading Suppliers & Manufacture for 19130-96-2 1-Deoxynojirimycin. ... Deoxynojirimycin inhibits mammalian glucosidase 1. As well, it inhibits intestinal and lysosmal alpha-glucosidases, beta- ... Recent studies show that the active ingredient of mulberry DNJ (l-deoxynojirimycin), only exists in mulberry leaves , by ... 1-100 Metric Ton/Month. Hangzhou Dayangchem Co., Ltd.. Contact Supplier Mulberry Leaf Extract. Cas No: 19130-96-2. USD $ 27.0- ...
duvoglustat hcl, duvoglustat hydrochloride, deoxynojirimycin hydrochloride, 1-deoxynojirimycin hydrochloride, unii-0rn23c42qr, ... duvoglustat hcl, duvoglustat hydrochloride, deoxynojirimycin hydrochloride, 1-deoxynojirimycin hydrochloride, unii-0rn23c42qr, ... duvoglustat hcl, duvoglustat hydrochloride, deoxynojirimycin hydrochloride, 1-deoxynojirimycin hydrochloride, unii-0rn23c42qr, ... duvoglustat hydrochloride usan, +-1-deoxynojirimycin hydrochloride, moranoline hydrochloride, 1-deoxy-l-altronojirimycin ...
Buy N-5-Carboxypentyl-1-deoxynojirimycin - CAS Number 79206-51-2 from LGC Standards. Please login or register to view prices, ... InChI=1S/C12H23NO6/c14-7-8-11(18)12(19)9(15)6-13(8)5-3-1-2-4-10(16)17/h8-9,11-12,14-15,18-19H,1-7H2,(H,16,17)/t8-,9+,11-,12-/m1 ... OC[[email protected]@H]1[[email protected]@H](O)[[email protected]](O)[[email protected]@H](O)CN1CCCCCC(=O)O. ... Your punchout session will expire in 1 min 59 sec.. Select " ... 6-[(2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexanoic acid. ...
REFINED STRUCTURE FOR THE COMPLEX OF 1-DEOXYNOJIRIMYCIN WITH GLUCOAMYLASE FROM (ASPERGILLUS AWAMORI) VAR. X100 TO 2.4 ANGSTROMS ... Interactions of 1-deoxynojirimycin with the enzyme at its principal site involve Arg 45, Asp 55, Arg 305, and carbonyl 177. In ... 1-DEOXYNOJIRIMYCIN. MORANOLINE. C6 H13 N O4. LXBIFEVIBLOUGU-JGWLITMVSA-N. ... The other 1-deoxynojirimycin molecule is associated with weak electron density and therefore, probably represents a binding ...
An edible fat-continuous emulsion comprising 1-deoxynojirimycin (DNJ) and lecithin, wherein the lecithin comprises ... deoxynojirimycin is commonly abbreviated in literature as "DNJ". The lUPAC name for it is: (2R,3R,4R,5S)-2-(hydroxymethyl) ... deoxynojirimycin (DNJ), on the emulsion. For reasons of emulsion stability, mouthfeel, and efficacy in DNJ release in the ... deoxynojirimycin (generally abbreviated as "DNJ") is a potent o glucosidase inhibitor, and as such may suppress postprandial ...
Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase. J Biol Chem 273: 26522-26527. ... deoxynojirimycin (AMP-DNM) that inhibits glucosylceramide synthase. Here, we treated the liver hepatoma cell line HepG2 with ... deoxynojirimycin Induces Sterol Regulatory Element-Binding Protein-Regulated Gene Expression and Cholesterol Synthesis in HepG2 ... deoxynojirimycin; SREBP, sterol regulatory element-binding protein; DMEM/HAMF-12, Dulbeccos modified Eagles medium/Hams ...
1-deoxynojirimycin-1-sulfonic acid ligand page. Quantitative data and detailed annnotation of the targets of licensed and ...
Boc Sciences offers cas 73285-50-4 1-Deoxynojirimycin HCl in bulk,please inquire us to get a quote for 73285-50-4 1- ... 1,5-Dideoxy-1,5-imino-D-sorbitol hydrochloride; (2R,3R,4R,5S)-2-(Hydroxymethyl)-3,4,5-piperidinetriol hydrochloride; ... 1,2,3-Tri-O-benzyl-4,6-O-benzylidene-a-D (CAS: 57783-75-2) ... It is commonly abbreviated as: C1V1 = C2V2 ... US & Canada (Toll free): 1-844-BOC(262)-0123 International: 1-631-504-6093 Europe: 44-203-286-1088 ...
Deoxynojirimycin derivatives and their uses as glucosylceramidase inhibitors CA2252238A1 (en) 1997-10-31. 1999-04-30. Sun ... deoxynojirimycin. medicament. diseases. manufacture. Prior art date. 1998-12-10. Application number. DK99967135T. Other ... DK99967135T 1998-12-10 1999-12-08 The use of long chain N-alkyl derivatives of deoxynojirimycin for the manufacture of a ... The use of long chain N-alkyl derivatives of deoxynojirimycin for the manufacture of a medicament for the treatment of diseases ...
1-Deoxynojirimycin (1-DNJ) is a naturally occurred sugar analogue with unique bioactivities. It was found in mulberry leaves ... 1-Deoxynojirimycin and its Derivatives: A Mini Review of the Literature Author(s):. Haijun Wang, Yin Shen, Lei Zhao* and Youfan ... 1-DNJ is a potent α-glucosidase inhibitor and it possesses anti-hyperglycemic, anti-obese, anti-viral and anti-tumor features. ... Some derivatives of 1-DNJ, like miglitol, miglustat and migalastat, were applied clinically to treat diseases such as diabetes ...
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Deoxynojirimycin / Mulberry Leaf Extract / 1-DNJ Other names: 1-Deoxynojirimycin (1-DNJ), Mulberry Leaf Extract, DNJ, 1-DNJ ... Deoxynojirimycin / Mulberry Leaf Extract / 1-DNJ. Other names: 1-Deoxynojirimycin (1-DNJ), Mulberry Leaf Extract, DNJ, 1-DNJ. ... Product standard: 1%, 2%,10%, 15% and customized. Test method: HPLC/ ELSD. Main Functions:. 1. Reducing blood fat, reducing ... Active ingredients: 1-Deoxynojirimycin. CAS No.: 9130-96-2. Appearance: Brown powder. ...
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Deoxynojirimycin(DNJ) is a kind of alkaloid present in Mulberry leaves and root bark. DNJ is naturally occurs in in other ... 1-Deoxynojirimycin(DNJ) is a kind of alkaloid present in Mulberry leaves and root bark.DNJ is approved to have effects on ... 1-Deoxynojirimycin(DNJ) is one of alkaloid present in Mulberry leaves and root bark. DNJ is naturally occurs in other plants ... What is 1-Deoxy nojirimycin(DNJ)?. 1-Deoxynojirimycin(1-DNJ), hereinafter referred to as DNJ, is a powerful α-glucosidase ...
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1-Deoxynojirimycin. Antiviral Agents. Anti-Infective Agents. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action ... or myocardial infarction within the 3 months before Visit 1 ... Visit 1), which is ,30 mL/min/1.73m2 ...
1-DEOXYNOJIRIMYCIN. C6 H13 N O4. LXBIFEVIBLOUGU-JGWLITMVSA-N. Ligand Interaction. ... Crystal structure of alpha-galactosidase A at pH 4.5 complexed with 1-deoxygalactonijirimycin. *DOI: 10.2210/pdb3GXT/pdb ... We compare our results with analogous experiments using alpha-Gal A and the chaperone 1-deoxygalactonijirimycin (DGJ), ...
Stage 1 includes a screening period of up to 2 months followed by a 6-month treatment period which will involve 4 visits to the ... Subjects who complete both Stage 1 and Stage 2 of the study as scheduled may be offered the opportunity to participate in an ... 1-Deoxynojirimycin. Antiviral Agents. Anti-Infective Agents. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action ... A follow-up visit will be undertaken 1 month following completion or discontinuation from the open-label treatment extension. ...
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Full text: Available Index: LILACS (Americas) Main subject: 1-Deoxynojirimycin / Tilapia / Probiotics Language: English Journal ... 1-Deoxynojirimycin from Bacillus subtilis can be used to improve the growth performance of juvenile Y. tilapia by affecting its ... 1-Deoxynojirimycin from Bacillus subtilis improves antioxidant and antibacterial activitie 1-Deoxynojirimycin from Bacillus ... Bacillus subtilis, as a probiotic, may have beneficial effects on Y. tilapia with compound 1-deoxynojirimycin (DNJ), which has ...
  • 1-Deoxynojirimycin (DNJ), also called duvoglustat or moranolin, is an alpha-glucosidase inhibitor, most commonly found in mulberry leaves. (wikipedia.org)
  • One inhibitor molecule is associated with strong electron density and represents the principal site of interaction of 1-deoxynojirimycin with the enzyme. (rcsb.org)
  • In addition, a water molecule (water 500) hydrogen bonds to Glu 400 and the 6-hydroxyl of 1-deoxynojirimycin and is at an approximate distance of 3.3 A from the "anomeric" carbon of the inhibitor. (rcsb.org)
  • 1-DNJ is a potent α-glucosidase inhibitor and it possesses anti-hyperglycemic, anti-obese, anti-viral and anti-tumor features. (currentmedicinalchemistry.com)
  • We report here that 1-deoxy-galactonojirimycin (DGJ), a potent competitive inhibitor of alpha-Gal A, effectively enhanced alpha-Gal A activity in Fabry lymphoblasts, when administrated at concentrations lower than that usually required for intracellular inhibition of the enzyme. (nih.gov)
  • 7 The first class, which contains the family 1 enzyme almond β-glucosidase, binds the inhibitor in the neutral form and then uses an active site carboxylate to protonate it. (rsc.org)
  • 8 One way of distinguishing between these two modes of inhibitor binding is that only the second class bind inhibitors with a permanent positive charge, such as glycosyl pyridinium ions or quaternary ammonium compounds such as the dimethylated analogue of 1-deoxynojirimycin. (rsc.org)
  • We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal α-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. (portlandpress.com)
  • July 20, 2007 - The US Food and Drug Administration (FDA) has granted orphan drug designation for mifepristone for the treatment of Cushing's syndrome , 1-deoxynojirimycin hydrochloride for the treatment of Pompe disease , and cetuximab for the treatment of pancreatic cancer . (medscape.com)
  • On June 18, the FDA granted orphan drug designation to 1-deoxynojirimycin hydrochloride (Amicus Therapeutics, Inc) for the treatment of Pompe disease, an inherited lysosomal storage disorder caused by a mutation that alters the structure and stability of α-glucosidase (Gaa), an enzyme responsible for the breakdown of glycogen. (medscape.com)
  • 3. The method as recited in claim 1, wherein said α1-antitrypsin dry powder is greater than about 50% pure. (google.com.au)
  • 4. The method as recited in claim 1, wherein said α1-antitrypsin dry powder is greater than about 90% pure. (google.com.au)
  • 7. The method of claim 1, wherein said α1-antitrypsin dry powder comprises aggregates of particles, wherein said particles have a mean particle size of from about 1 μm to about 5 μm and said aggregates have a mean size of from about 50 μm to about 600 μm, and wherein said aggregates have a friability index of from about 10 to about 60. (google.com.au)
  • Interactions of 1-deoxynojirimycin with the enzyme at its principal site involve Arg 45, Asp 55, Arg 305, and carbonyl 177. (rcsb.org)
  • Serum levels of interleukin (IL) -1 , IL-6 and IL-10 were studied by enzyme-linked immunosorbent assay (ELISA). (bireme.br)
  • For the treatment of adult patients with mild to moderate type 1 (nonneuropathic) Gaucher's disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access). (drugbank.ca)
  • Acid alpha-glucosidase , also called α-1,4-glucosidase and acid maltase , is an enzyme ( EC 3.2.1.20 ) that helps to break down glycogen in the lysosome . (wikipedia.org)
  • This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. (wikipedia.org)
  • Acid alpha-1,4-glucosidase is a lysosomal enzyme that hydrolyzes the alpha-1,4 and alpha-1,6 linkages of its natural substrate, glycogen at acid pH. (dovepress.com)
  • The enzyme appears to be expressed in most tissues, 1 including skeletal muscle, diaphragm, heart, placenta, kidneys, and central nervous system (CNS), predominantly in the spinal cord and brain stem Schwann cells and neuronal cell, including the anterior horn cells. (dovepress.com)
  • Its compound called 1-deoxynojirimycin (DNJ) binds to an enzyme that converts starches into glucose, helping it go through the intestine instead of being absorbed as sugar. (naturalnews.com)
  • Taking 1 gram of the powdered leaf three times a day for 4 weeks decreased fasting blood sugar levels by 27%, compared with an 8% decrease with the diabetes medicine glyburide , 5 mg daily. (webmd.com)
  • For diabetes: 1 gram of the powdered leaf taken three times daily. (webmd.com)
  • Diabetes mellitus is a chronic disease in which the body does not produce enough insulin to function properly (type 1) or body cells do not react to insulin (insulin resistance) (type 2). (springer.com)
  • Type 1 diabetes is caused by T cell-mediated autoimmune destruction of insulin-producing cells in the pancreas. (jove.com)
  • Induced islet neogenesis by gene transfer of Neuogenin3 (Ngn3), the islet lineage-defining specific transcription factor and Betacellulin (Btc), an islet growth factor has the potential to cure type 1 diabetes. (jove.com)
  • According to the International Diabetes Federation (IDF) report in 2013, there were 382 million people living with diabetes worldwide, and this rate was expected to increase 592 million by 2035 [ 1 ]. (alliedacademies.org)
  • Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase , phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxan-induced diabetic mice. (thefreedictionary.com)
  • The distinct effect exerted by various glycosidase inhibitors (e.g. 1-deoxynojirimycin, N-methyl-dNM, 1-deoxymannojirimycin) on the electrophoretic mobility of the pp-α-F 3 polypeptide indicates that its oligosaccharide chains are processed to presumbly Man 9 -GlcNAc 2 structures under the in vitro conditions of translation. (bioscirep.org)
  • 9 Nojirimycins could be reasonably expected to be transition state (TS) analogue inhibitors, as 1 , when protonated, clearly resembles the glucosylium ion 4 ( Fig. 1 ), which is quite similar to the TS of acidic or spontaneous glycoside hydrolysis. (rsc.org)
  • Emulsion according to claim 1 or 2, wherein the emulsion comprises from 0.002 to 0.05 % by weight, preferably from 0.003 to 0.04 % by weight on the emulsion of 1-deoxynojirimycin (DNJ). (sumobrain.com)
  • 10 The Withers group addressed the mimicry of iminosugar 1 and castanospermine to the TS of Agrobacterium β-glucosidase (GH1 family). (rsc.org)
  • As a dietary supplement, take one (1) capsule twice daily immediately before the heaviest carbohydrate or sugar containing meals/drinks, or as recommended by a healthcare practitioner. (acuatlanta.net)
  • In 1963, HG Cori classified it as glycogen storage disease type II and, following the discovery of the lysosome by de Duve, Hers determined that the intra-lysosomal glycogen deposition was secondary to a deficiency of acid alpha-1,4 glucosidase (acid maltase), thus the first known lysosomal storage disorder. (dovepress.com)
  • 10. Use of the emulsion according to any of claims 1 to 8, wherein the emulsion is combined with edible matter comprising carbohydrates, in such an amount that the resulting foodstuff contains from 0.001 to 0.03 wt % of 1-deoxynojirimycin (DNJ) on carbohydrate basis. (sumobrain.com)
  • Of the 56 up-regulated genes, 17 were direct target genes for transcription factors sterol regulatory element-binding protein (SREBP) 1 or SREBP2, which activate genes in the sterol biosynthesis pathway. (aspetjournals.org)
  • MAN2B1 (Mannosidase Alpha Class 2B Member 1) is a Protein Coding gene. (genecards.org)
  • As a consequence of this improved function of fat tissue we observed less inflammation, which was characterized by reduced numbers of adipose tissue macrophages (crown-like structures) and reduced levels of the macrophage chemo attractants monocyte-chemoattractant protein-1 (Mcp-1/Ccl2) and osteopontin (OPN). (nih.gov)
  • [1] This gene encodes a lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. (wikidoc.org)
  • Cystic fibrosis (CF) is a fatal autosomal-recessive genetic disorder caused by loss-of-function mutations in the CFTR gene, which encodes for the CFTR protein (CF transmembrane conductance regulator) ( 1 , 2 ). (pnas.org)
  • Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. (bvsalud.org)
  • growth hormone (gh), growth hormone receptor (ghr), insulin-like growth factor 1 (igf-1), insulin-like growth factor receptor (igf-1r), insulin-like growth factor binding protein 1 (igfbp-1), ghrelin (ghrl), cholecystokinin (cck) and glucokinase (gck), thyroglobulin (tg). (thefreedictionary.com)
  • To restore or improve CFTR function in the majority of the population of patients with CF, it will likely be necessary to target the underlying molecular defect in CFTR caused by the F508del CFTR mutation, which is present in 90% of patients with CF ( 1 , 11 ). (pnas.org)
  • Molecular Neurodegeneration, 12(1), 52. (mbfbioscience.com)
  • Molecular Neurobiology, 1-11. (mbfbioscience.com)
  • For PC-12 cells pretreated with 1-deoxymannojirimycin at 1mM for 72h, thawed cell viability after more than 8-w cryopreservation at -80 degrees C in 10% (v/v) dimethyl sulfoxide was much higher than that for cells without pretreatment. (biomedsearch.com)
  • cells in diabetic mice, and that the anti-hyperglycemic efficacy of this combination was better than that of 1-deoxynojirimycin (DNJ) or polysachharide alone. (jove.com)
  • Moranolineor 1-DNJ holds back complex carbohydrates, starches, maltose and sucrose from breaking down into glucose. (pe-factory.com)
  • Morus alba L. was used as Chinese traditional medicine for hundreds of years and its fruit, mulberry, has been proved to have high nutritional value and perfect healthy function [ 1 ]. (alliedacademies.org)