期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 5, 页码 2367-2377出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm501872s
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资金
- National Institute of General Medical Sciences of the United States National Institutes of Health [GM-068649]
The emergence of antibiotic-resistant infections highlights the need for novel antibiotic leads, perhaps with a broader spectrum of activity. Herein, we disclose a semisynthetic, catalytic approach for structure diversification of vancomycin. We have identified three unique peptide catalysts that exhibit site-selectivity for the lipidation of the aliphatic hydroxyls on vancomycin, generating three new derivatives 9a, 9b, and 9c. Incorporation of lipid chains into the vancomycin scaffold provides promising improvement of its bioactivity against vancomycin-resistant enterococci (Van A and Van B phenotypes of VRE). The MICs for 9a, 9b, and 9c against MRSA and VRE (Van B phenotype) range from 0.12 to 0.25 mu g/mL. We have also performed a structure-activity relationship (SAR) study to investigate the effect of lipid chain length at the newly accessible G(4)-OH derivatization site.
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