| Autor: |
Goldman RC; Incara Research Laboratories, 8 Cedar Brook Drive, Cranbury, NJ 08512, USA. rgoldman@irl.incara.com, Baizman ER, Longley CB, Branstrom AA |
| Jazyk: |
angličtina |
| Zdroj: |
FEMS microbiology letters [FEMS Microbiol Lett] 2000 Feb 15; Vol. 183 (2), pp. 209-14. |
| DOI: |
10.1111/j.1574-6968.2000.tb08959.x |
| Abstrakt: |
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: |
MEDLINE |
| Externí odkaz: |
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