Vancomycin mimicry: towards new supramolecular antibiotics

Vancomycin is the best-known of the glycopeptide group antibiotics (GPAs), a family of agents which operate by binding the C-terminal deptide d-Ala-d-Ala. This anionic epitope is an interesting target because it plays a central role in bacterial cell wall synthesis, and is not readily modified by evolution. Accordingly, vancomycin has been in use for >60 years but has only provoked limited resistance. Agents which mimic vancomycin but are easier to synthesise and modify could serve as valuable weapons against pathogenic bacteria, broadening the scope of the GPAs and addressing the resistance that does exist. This article gives an overview of vancomycin's structure and action, surveys past work on vancomycin mimicry, and makes the case for renewed effort in the future.