A new strong inhibitor of beta-mannosidase
ABSTRACT N-phenyl-carbamate of D-mannonohydroxymolactone (I) was synthesized from mannose and was shown to be the best competitive inhibitor of beta-mannosidase so far reported (Ki = 25 nM).
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ABSTRACT: The subunit composition of the extracellular complex from Clostridium thermocellum was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Twenty-six bands, representing proteins with apparent molecular sizes ranging from 37,500 to 185,000 Da, could be detected by silver staining. Cultivation of the bacteria with the substrate Avicel, Sigma cellulose, Solka floc, or cellobiose as the carbon source had no influence on the number of detectable protein bands. By activity staining with the substrate carboxymethyl cellulose or xylan added to the SDS-polyacrylamide gels, 15 of the 26 bands exhibited endoglucanase activity and 13 showed xylanase activity. In 8 of the 26 bands, both activities could be found. As minor activities, beta-glucosidase, beta-xylosidase, beta-galactosidase, and beta-mannosidase activities could be demonstrated in the cellulase complex. Upon measuring the release of para-nitrophenol (PNP) from PNP-cellobioside and determining the amount of glucose formed, the presence of exoglucanase activity was indicated. Upon glycoprotein staining of SDS-polyacrylamide gels, 14 of the 26 bands reacted positive, indicating the glycoprotein nature of the respective proteins. Four proteins (apparent molecular sizes, 58,000, 72,500, 94,000, and 110,000 Da) could be enriched from the originally bound cellulase complex by preparative SDS-PAGE. The two smaller proteins exhibited xylanase activity, whereas the 94,000-Da protein had endo- and exoglucanase activity, and the 110,000-Da protein degraded PNP-pyranosides.Applied and Environmental Microbiology 01/1991; 56(12):3798-804. · 3.95 Impact Factor
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ABSTRACT: Glycosidase inhibitors are moving increasingly out of the laboratory and into the clinic as potential agents for the treatment of diseases including diabetes, AIDS and cancer. These compounds, originally isolated from natural sources and utilized for unraveling the glycosylation pathways involved in post-translational modification of glycoproteins, have multiple effects that are only now being fully appreciated. In addition to their ability to inhibit processing exoglycosidases, lysosomal glycosidases and the intestinal disaccharidases involved in carbohydrate digestion, these compounds appear to have additional activities, including immunomodulatory properties and inhibition of glycolipid synthesis, which continue to expand their range of potential uses.Current Opinion in Structural Biology 11/1995; 5(5):605-11. DOI:10.1016/0959-440X(95)80051-4 · 8.75 Impact Factor
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ABSTRACT: At pH 4.5 (citrate buffer), D-gluconhydroximo-lactone (2), the N-methylurethane 3 and the N-phenylurethane 4 inhibit competitively the hydrolysis of p-nitrophenyl β-D-glucopyranoside by emulsin. The IC50 values of 2, 3, and 4 were 1.6 × 10−4, 1.0 × 10−4, and 5.8 × 10−6M, respectively. The Ki values of 2 and 4 were 9.8 × 10−5 and 2.3 × 10−6M, respectively, while D-glucono-1,5-lactone (1) showed IC50 = 1.1 × 10−4M and Ki = 3.7 × 10−5M.Helvetica Chimica Acta 03/1986; 69(2):267-270. DOI:10.1002/hlca.19860690203 · 1.39 Impact Factor