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.
Bauke Albada
H
H
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Arnusch
Christopher J
CJ
Branderhorst
Hilbert M
HM
Verel
Anne-Marie
AM
Janssen
Wouter T M
WT
Breukink
Eefjan
E
de Kruijff
Ben
B
Pieters
Roland J
RJ
Liskamp
Rob M J
RM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D002462:Cell Membrane / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry; D006868:Hydrolysis; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019287:Zinc Sulfate / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D050091:Dendrimers; D007093:Imidazoles; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D014640:Vancomycin; D019287:Zinc Sulfate