title: The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant Enterococci.
abstract: Lipid II is a crucial component in bacterial cell wall synthesis [Breukink, E., et al. (1999) Science 286, 2361-2364]. It is the target of a number of important antibiotics, which include vancomycin and nisin [Breukink, E., and de Kruijff, B. (2006) Nat. Rev. Drug Discovery 5, 321-332]. Here we show that a hybrid antibiotic that consists of vancomycin and nisin fragments is significantly more active than the separate fragments against vancomycin resistant entercocci (VRE). Three different hybrids were synthesized using click chemistry and compared. Optimal spacer lengths and connection points were predicted using computer modeling.
authors.affiliation: Department of Chemical Biology and Organic Chemistry, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Arnusch
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Verel
authors.forename: Wouter T M
authors.initials: WT
authors.lastname: Jansen
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Ben
authors.initials: B
authors.lastname: de Kruijff
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
authors.forename: Eefjan
authors.initials: E
authors.lastname: Breukink
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004338:Drug Combinations; D016983:Enterococcus / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009561:Nisin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D014640:Vancomycin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D009561:Nisin; D014640:Vancomycin