Cooperative binding interactions of glycopeptide antibiotics.

Glycopeptide antibiotics of the vancomycin group bind to bacterial cell wall analogue precursors, and typically also form dimers. We have studied the interplay between these two sets of noncovalent bonds formed at separate interfaces. Indole-2-carboxylic acid (L) forms a set of hydrogen bonds to the glycopeptide antibiotic chloroeremomycin (CE) that are analogous to those formed by N-Ac-D-Ala. The ligand/CE dimer interactions (in L/CE/CE/L) are shown to occur with positive cooperativity and structural tightening at the dimer interface. From theoretical considerations and from other data, it is inferred, but not proven, that in the exercise of positive cooperativity, the interface that will be tightened to the greatest degree is the one that lies in the shallowest free energy well.