DISSECTION OF THE CONTRIBUTIONS TOWARD DIMERIZATION OF GLYCOPEPTIDE ANTIBIOTICS

A procedure for the determination of association constants in aqueous solution using hydrogen-deuterium exchange has been developed and used to measure the dimerization constant, K-dim, for a number of strongly dimerizing glycopeptide antibiotics. These values provide further insight into the thermodynamic contributions of various structural epitopes to the dimerization of these antibiotics. Consideration of ligand binding affinities together with dimerization potentials provides evidence that dimerization is implicated in the physiological mode of action of these antibiotics.