TY - JOUR
T1 - 19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance
AU - Entress, Richard M. H.
AU - Dancer, Robert J.
AU - O'Brien, Dominic P.
AU - Try, Andrew C.
AU - Cooper, Matthew A.
AU - Williams, Dudley H.
PY - 1998/6
Y1 - 1998/6
N2 - 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.
AB - 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.
KW - F NMR
KW - Glycopeptides
KW - Model bacterial cell-wall surfaces
KW - VanA and VanB resistance
UR - http://www.scopus.com/inward/record.url?scp=0031595843&partnerID=8YFLogxK
U2 - 10.1016/S1074-5521(98)90171-5
DO - 10.1016/S1074-5521(98)90171-5
M3 - Article
C2 - 9653551
AN - SCOPUS:0031595843
SN - 1074-5521
VL - 5
SP - 329
EP - 337
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 6
ER -