Interactions of alpha- and beta-avoparcin with bacterial cell-wall receptor-mimicking peptides studied by electrospray ionization mass spectrometry.

Solution phase affinity constants of the glycopeptide antibiotic alpha- and beta-avoparcin, with a range of bacterial cell-wall receptor-mimicking model peptides, were determined by a relatively new method: affinity electrospray ionization mass spectrometry (ESI-MS). This method is relatively efficient and allows the parallel determination of several affinity constants in mixtures of antibiotics and receptors. The determined binding constants for alpha- and beta-avoparcin were compared with those of the related glycopeptide antibiotic vancomycin. The solution phase binding affinities of alpha- and beta-avoparcin on one hand, and vancomycin on the other, were found to be in the same order, at least for the range of receptor-mimicking peptides studied. However, beta-avoparcin displayed slightly higher binding affinities than alpha-avoparcin, particularly for strong binding receptor-mimicking peptides. The evidence that alpha- and beta-avoparcin and vancomycin are structurally similar, combined with the present data revealing their similar affinity for bacterial cell-wall receptor-mimicking peptides, supports the hypothesis that the appearance of vancomycin-resistant enterococci (VRE) might be linked to the widespread use of avoparcin.