19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance.
| Autor: | Entress RM; Cambridge Centre for Molecular Recognition, University Chemical Laboratory, UK., Dancer RJ, O'Brien DP, Try AC, Cooper MA, Williams DH |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Chemistry & biology [Chem Biol] 1998 Jun; Vol. 5 (6), pp. 329-37. |
| DOI: | 10.1016/s1074-5521(98)90171-5 |
| Abstrakt: | 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 depsipeptides that are anchored into vesicles) relative to those measured in free solution. Conclusions: Surface-enhanced binding, previously shown for strongly dimerizing 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 maximizing this enhancement. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|