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Vancomycin-Teixobactin Conjugates
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DOI：10.1021/jacs.4c17175.png)
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Abstract
En 中文
Vancomycin continues to be a widely used antibiotic of last resort in treating drug-resistant pathogens despite the emergence of vancomycin-resistant strains such as vancomycin-resistant Enterococci (VRE). This communication reports that conjugation of vancomycin to a second antibiotic that targets a different region of lipid II enhances and rescues its antibiotic activity. Conjugation of vancomycin to a minimal teixobactin pharmacophore in which residues 1-6 are replaced with an aromatic amide results in substantial enhancement in activity over the individual components or mixtures thereof. Three conjugates with minimum inhibitory concentrations (MICs) of 0.5 mu g/mL against methicillin-resistant Staphylococcus aureus (MRSA) and 0.063-0.125 mu g/mL against methicillin-susceptible Staphylococcus aureus (MSSA) were identified. Each of these conjugates is also active against VRE, even though the individual components are inactive, with the most active conjugate (Cbp-Lys10-teixo7-11-vanco) having an MIC of 2-4 mu g/mL. These findings demonstrate that conjugation of vancomycin to a minimal teixobactin pharmacophore is an effective strategy for enhancing the activity of vancomycin against important Gram-positive pathogens.
Keywords:
ALA-D-ALA
RESISTANCE
MECHANISM
BINDING
IMPACT
Journal
IF:
15.6
Papers:
20.0W
Citations:
60.2W
Organization
Cited Papers
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