Subtle differences in molecular recognition between modified glycopeptide antibiotics and bacterial receptor peptides identified by electrospray ionization mass spectrometry

Abstract

In determining structure–activity relationships, it is advantageous if binding constants for a variety of ligands to a given target molecule can be directly obtained from a single aqueous solution containing a mixture of ligands and the target molecule. In this paper further evidence is provided showing that electrospray ionization mass spectrometry (ESI-MS) can be used in the rapid quantitative analysis of mixtures of vancomycin-group antibiotics and their bacterial cell-wall receptors allowing the identification of even subtle differences in binding constants. Differences in affinities are quantified for a mixture of vancomycin antibiotics (vancomycin, dechlorovancomycin and N-demethylvancomycin) and for a mixture of ristocetin A and its pseudoaglycone. Binding constants determined by ESI-MS were found to be in close agreement with those determined by more direct methods in aqueous solution.