Antibody-catalyzed cleavage of the D-Ala-D-Lac depsipeptide: an immunological approach to the problem of vancomycin resistance.
Vancomycin resistance is currently a major healthcare problem. The development of a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac depsipeptide provides a potentially novel antibiotic strategy. A phosphonate hapten design was used to program antibody catalysis. The characteristics of the hapten were shown to be important for obtaining a viable immune response and several catalytic mAbs that cleave a peptidoglycan model substrate. The best mAb afforded a >500-fold rate enhancement over background.
Isomura
Shigeki
S
The Scripps Research Institute and the Skaggs Institute for Chemical Biology, Department of Chemistry, La Jolla, CA 92037, USA.
Ashley
Jon A
JA
Wirsching
Peter
P
Janda
Kim D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D002384:Catalysis; D004151:Dipeptides / Q000737:chemistry* / Q000276:immunology; D004351:Drug Resistance; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D063065:Organophosphonates; D014640:Vancomycin
D000911:Antibodies, Monoclonal; D004151:Dipeptides; D006241:Haptens; D063065:Organophosphonates; D014640:Vancomycin