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.