Phosphorodithioates:: synthesis and evaluation of new haptens for the generation of antibody acyl transferases

An extension of the transition state analogue (TSA) hapten approach for the elicitation of catalytic antibodies for acyl-transfer reactions is described. It is based on the enlistment of phosphorodithioate 1 as a stable mimic of the putative tetrahedral intermediate (TI-) formed during the base-catalyzed hydrolysis of bisaryl carbonate 2. Six members of a library of 25 monoclonal antibodies elicited to 1 catalyze the hydrolysis of 2. The most efficient catalyst, 48F10, exhibits Michaelis-Menten kinetics [K-m(2)=686 mu M, k(cat)(2)=2.7 min(-1), k(cat)(2)/k(uncat)(2)=3 x 10(4)] and is one of the most active carbonate hydrolyzing antibodies yet reported. This report highlights the utility of haptens that incorporate substitution of the non-bridging phosphorus(V) oxygen atoms present in the more classical TSA approaches with sulfur, to elicit efficient catalysts for acyl-transfer processes. (C) 1999 Elsevier Science Ltd. All rights reserved.