Potential scorpionate antibiotics: targeted hydrolysis of lipid II containing model membranes by vancomycin-TACzyme conjugates and modulation of their antibacterial activity by Zn-ions.

The antibiotic vancomycin-that binds lipid II in the bacterial cell membrane-was conjugated to a mono- and tetravalent mimic of the tris-histidine catalytic triad of metalloenzymes. Targeted hydrolysis by the conjugate was observed using model membranes containing lipid II, and in vitro MIC-values of the targeted mimic constructs could be modulated by Zn-ions.

The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant Enterococci.

Lipid II is a crucial component in bacterial cell wall synthesis [Breukink, E., et al. (1999) Science 286, 2361-2364].