19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance

Richard M. H. Entress, Robert J. Dancer, Dominic P. O'Brien, Andrew C. Try, Matthew A. Cooper, Dudley H. Williams*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Background: The emergence of bacteria that are resistant to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, has made the study of the binding characteristics of glycopeptides to biologically relevant depsipeptides important. These depsipeptides, terminating in -D-alanyl-D-lactate, mimic the cell-wall precursors of resistant bacteria. Results: The use of 19F-labelled ligands in the study of the therapeutically important vancomycin series of antibiotics is demonstrated. The substantial simplification of spectra that occurs when such labelled ligands are employed is used in the measurement of binding affinities of depsipeptides to chloroeremomycin (CE). Large enhancements of binding affinities are found at a model bacterial cell-wall surface (constituted from depsipetides that are anchored into vesicles) relative to those measured in free solution. Conclusions: Surface-enhanced binding, previously shown for strongly dimerising glycopeptide antibiotics to normal -D-alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to the surface of models of VanA- and VanB-resistant bacteria. The effect of depsipeptide chain length is shown to be critically important in producing and maximising this enhancement.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalChemistry and Biology
Volume5
Issue number6
DOIs
Publication statusPublished - Jun 1998
Externally publishedYes

Keywords

  • F NMR
  • Glycopeptides
  • Model bacterial cell-wall surfaces
  • VanA and VanB resistance

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