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

In determining structure-activity relationships, it is advantageous if bind ing constants for a variety of ligands to a given target molecule can be di rectly obtained from a single aqueous solution containing a mixture of liga nds and the target molecule. In this paper further evidence is provided sho wing that electrospray ionization mass spectrometry (ESI-MS) can be used in the rapid quantitative analysis of mixtures of vancomycin-group antibiotic s and their bacterial cell-wall receptors allowing the identification of ev en subtle differences in binding constants. Differences in affinities are q uantified for a mixture of vancomycin antibiotics (vancomycin, dechlorovanc omycin 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 sol ution.