Chlorobiphenyl-desleucyl-vancomycin inhibits the transglycosylation process required for peptidoglycan synthesis in bacteria in the absence of dipeptide binding
| Autor: | Arthur A. Branstrom, Eugene R. Baizman, Clifford B. Longley, Robert C. Goldman |
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| Rok vydání: | 2000 |
| Předmět: |
Glycosylation
Dipeptide Bacteria Lipid II Stereochemistry Biological activity Dipeptides Peptidoglycan Biology Microbiology Glycopeptide Anti-Bacterial Agents carbohydrates (lipids) chemistry.chemical_compound chemistry Biosynthesis Mechanism of action Biochemistry Vancomycin Genetics medicine medicine.symptom Molecular Biology Antibacterial agent |
| Zdroj: | FEMS Microbiology Letters. 183:209-214 |
| ISSN: | 1574-6968 0378-1097 |
| Popis: | Novel glycopeptide analogs are known that have activity on vancomycin resistant enterococci despite the fact that the primary site for drug interaction, D-ala-D-ala, is replaced with D-ala-D-lactate. The mechanism of action of these compounds may involve dimerization and/or membrane binding, thus enhancing interaction with D-ala-D-lactate, or a direct interaction with the transglycosylase enzymes involved in peptidoglycan polymerization. We evaluated the ability of vancomycin (V), desleucyl-vancomycin (desleucyl-V), chlorobiphenyl-vancomycin (CBP-V), and chlorobiphenyl-desleucyl-vancomycin (CBP-desleucyl-V) to inhibit (a) peptidoglycan synthesis in vitro using UDP-muramyl-pentapeptide and UDP-muramyl-tetrapeptide substrates and (b) growth and peptidoglycan synthesis in vancomycin resistant enterococci. Compared to V or CBP-V, CBP-desleucyl-V retained equivalent potency in these assays, whereas desleucyl-V was inactive. In addition, CBP-desleucyl-V caused accumulation of N-acetylglucosamine-beta-1, 4-MurNAc-pentapeptide-pyrophosphoryl-undecaprenol (lipid II). These data show that CBP-desleucyl-V inhibits peptidoglycan synthesis at the transglycosylation stage in the absence of binding to dipeptide. |
| Databáze: | OpenAIRE |
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