The role of the sugar and chlorine substituents in the dimerization of vancomycin antibiotics

Evidence is presented for the formation of dimers in aqueous solutions of the glycopeptide antibiotics eremomycin, A82846B, vancomycin, and eremomycin- psi . The dimerization constant K sub(dim) is determined by super(1)H NMR spectroscopy for the last two compounds and also for the related compound ristocetin- psi , for which dimerization has previously been reported in mixed solvents. Values of K sub(dim) are obtained for these compounds over a range of temperatures, and thus Delta H sub(dim) and Delta S sub(dim) are calculated. In addition, a lower limit for K sub(dim) in the case of eremomycin is calculated (10 super(5)/M). This is a remarkably large value, and it may be that dimerization is implicated in antibiotic action. The possibility that natural selection has led to adaptations which promote dimerization (such as the nature and sites of attachment of the sugars and a ring 2 chlorine atom) is discussed.