Two conformers of the glycopeptide antibiotic teicoplanin with distinct ligand binding sites.

The clinically important vancomycin group glycopeptide antibiotics, which act by blocking cell wall synthesis, are crucial in the treatment of methicillin resistant Staphylococcus aureus. All of the group members studied so far, with the apparent exception of teicoplanin, enhance their antibiotic action by the formation of an asymmetric homodimer. Teicoplanin exists in two main conformers which differ by a rotation of approximately 180 degrees of a sugar residue. From NMR studies and molecular modelling, we present structures for the two conformers and conclude that they have different binding affinities for cell wall analogues. The two conformers of teicoplanin are closely analogous to those adopted by each half of the asymmetric dimers of the other vancomycin group antibiotics.