Ab initio study toward designing transition-state analogues which elicit proteolytic catalytic antibodies

Abstract

New haptens useful for eliciting proteolytic antibodies are proposed. Transition state conformations of the amide and ester bond cleavages of simple quantum models were obtained by HF/6-31G* ab initio calculations. The results suggested that in our model of the transition state, forming the tetrahedral structure at the carbonyl carbon in a nucleophilic addition step is sufficient for ester bond cleavage, while formation of both the tetrahedral structure and the appropriate orientation of the lone-pair electrons on the nitrogen for the proton addition is necessary for amide bond cleavage. The key feature for designing good and/or potent haptens deduced from the transition state model could therefore be that both the tetrahedral conformation at the carbonyl carbon and proper orientation of lone pairs are simultaneously and appropriately reproduced in the haptens. Based on calculations, we designed potentially appropriate new haptens with the phosphonamidate functional group for eliciting proteolytic antibodies. Copyright