Glycopeptide inhibitor

Lectin bound soluble glycopeptide inhibitor washed away... 

Glycopeptides containing glycosyl L-aspara-gine, L-serine, and L-threonine, developments in, 50,277-310 Glycoside hydrolases, mechanistic information firm studies with reversible and irreversible inhibitors, 48, 319-384 Glycoside synthesis, anomeric-oxygen activation for (trichloroacetimidate method), 50,21 -123... 

Figure 14.8 (A) Screening of a glycopeptide library using a fluorescent-labeled lectin and ligands bound to PEGA beads. The acbve compounds are analysed by mass spectrometry. (B) FITC-labeled lectin binding to resin bound mannose could be inhibited by soluble glycopeptides obtained from library screen. Percent inhibition was quantified by recording of lectin fluorescence. Only every second well of the microtiter plate was used and nonfluorescent beads indicated good inhibitors.44...

Other inhibitors of cell wall synthesis. Bacitracin and vancomycin interfere with the transport of pepti-doglycans through the cytoplasmic membrane and are active only against gram-positive bacteria. Bacitracin is a polypeptide mixture, markedly nephrotoxic and used only topically. Vancomycin is a glycopeptide and the drug of choice for the (oral) treatment of bowel inflammations occurring as a complication of antibiotic therapy (pseudomembranous enterocolitis caused by Clostridium difficile), it is not absorbed. 

The glycopeptides are inhibitors of cell wall synthesis. They bind to the terminal carboxyl group on the d-alanyl-D-alanine terminus of the A-acetylglucosamine-A-acetylmuramic acid peptide and prevent polymerization of the linear peptidoglycan by peptidoglycan synthase. They are bactericidal in vitro. 

The replacement of the anomeric oxygen by a CF2 has been considered to obtain hydrolytically stable difluoro-C-glycosides, difluoro-C-disaccharides and difluoro-C-glycopeptides. These compounds have been synthesized [65-68], but their use as inhibitors does not seem to have been biologically validated. 

Staphylococcus aureus - [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [DISINFECTANTS AND ANTISEPTICS] (Vol 8) - [ANTIBIOTICS - BETA-LACTAMS - BETA-LACTAMASE INHIBITORS] (Vol 3) - [ANTIBIOTICS - LINCOSAMINIDES] (Vol3) - [ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHERS] (Vol 3) - [ANTIBIOTICS-AMINOGLYCOSIDES] (Vol2) - [ANTIBIOTICS - GLYCOPEPTIDES(DALBAHEPTIDES)] (Vol 2) -bacitracin resistance [ANTIBIOTICS - PEPTIDES] (Vol 3) -ethanol activity against [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -inhibited by sorbates [SORBIC ACID] (Vol 22)... 

Gao Y (2002) Glycopeptide Antibiotics and Development of Inhibitors to Overcome Vancomycin Resistance. Nat Prod Rep 19 100... 

Figure S. Enzymatic analysis of inhibitor glycopeptides. Glycopeptide and oligosaccharide products were isolated by ion-exchange and gel filtration techniques. Monosaccharide constituents were determined by GLC of their glycitol acetate derivatives following Dowex-SO [H J catalyzed acid hydrolysis ("26, 27). Liberated mannose was determined by direct GLC of its glycitol acetate A. niger a-l,2-mannosidase and fl-mannosidase were prepared by the procedures of Swami-nathan et al. (31) and Elbein et al. (32), respectively S. griseus endoglucosamini-dase teas prepared as described by Tarentino and Maley (33).

Figure 6. Inhibition of fi-galactosidase assimilation by inhibitor glycoproteins, glycopeptides, and derivatives. The open symbols represent data obtained with glycopeptides open squares, inhibitor glycoprotein fraction open circles, unit A glycopeptides prepared from thyroglobulin (30) and open triangle,unit B glycopeptides from thyroglobulin (30).

Attempts to Detect Mannose-6-Phosphate in B-Galactosidase and Inhibitor Glycopeptides. Although colorimetric analysis of the inhibitor glycopeptide fraction for phosphate proved negative, the occurrence of trace quantities of mannose phosphate could not be eliminated. Experiments were therefore undertaken to demonstrate the possible presence of small amounts of mannose-6-phosphate in B-galactosidase and in the inhibitor glycopeptide fraction. 

Figure 8. Radioactivity scan of a paper electrophoretogram of NaB[3H7 s reduced hydrolysate of inhibitor glycopeptides (top) and glycopeptides from fi-galactosidase (bottom). Phosphorylated compounds could not be detected in peaks A and B or in the mannitol-6-phosphate region, C. (see the text for details).

We have developed two methods for the synthesis of natural and unnatural products from D-glucose. Enantio-and diastereo-switching method established a new strategy for the synthesis of four possible stereomers for natural products synthesis, and this powerful method was successfully applied to the synthesis of unnatural protein phosphatase inhibitors. The second synthetic method involved the preparation of the urea-glycosidic linkages for the synthesis of glycopeptide mimics. 

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