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Surface-enhanced binding, previously shown for strongly dimerizing glycopeptide antibiotics to normal -D-alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to the surface of models of VanA- and VanB-resistant bacteria. The effect of depsipeptide chain length is shown to be critically important in producing and maximizing this enhancement.

The factors that give rise to binding enhancements when a strongly dimerizing vancomycin-group antibiotic (chloroeremomycin) binds to a model cell surface of vancomycin-resistant enterococci (VRE) have been semiquantitated. The model cell surface is comprised of vesicles to which have been anchored cell wall precursor analogues of vancomycin-resistant bacteria (which terminate in -d-lactate) via a hydrophobic docosanoyl (C22) chain. Using 1H and 19F NMR spectroscopy, a large binding enhancement at the model cell surface (compared to the binding of an analogous ligand in free solution) has been observed. This enhancement can be partitioned into two distinct factors:  a simple concentrating factor arising from an increase in local concentration of ligand when it is located at the vesicle surface and a factor arising from the cooperative interaction of species mutually bound to the membrane surface. The overall enhancement to binding at a surface compared to binding in free solution was found to be a factor of 102−103. In contrast, no significant surface binding enhancement was observed for the weakly dimerizing antibiotic vancomycin.

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