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.

Graphical abstractVancomycin was conjugated to a hydrolysis catalyst (or TACzyme). Targeted hydrolysis by such a conjugate was observed using membranes containing lipid II. MIC-values of targeted hydrolysis catalyst constructs could be modulated by Zn(II).Figure optionsDownload full-size imageDownload as PowerPoint slide