Esterolytic Catalytic Antibodies

Abstract

The concept of synthesizing stable analogs of the rate-limiting transition state for a given chemical reaction and then using these substances as haptens to raise antibodies which serve as specific catalysts for that reaction, has now been demonstrated for a considerable number of reactions [1]. Although this notion dates back to Pauling [2] and was first succintly state by Jencks [3], the field of catalytic antibodies may still be considered to be in its developmental stage ven though it represents the most succesful approach for achieving tailor-made catalysts and has been applied to some 100 different chemical reactions[1]. Perhaps because of the seemingly unlimited possibilities inherent in our ability to now “program” a specific catalyst for a given chemical reaction, and of the dramatic success of catalytic antibodies relative to all other current approaches for achieving enzyme-like catalysts, there is some quarters a sense of unfulfilled expectation: one is asked, why have catalytic antibodies not yet found applications in medicine or chemistry or biology? The recent milestones in the development of catalytic antibodies have been recorded [4] and one catalytic antibody has recently entered the marketplace as a chemical reagent [5]; this antibody catalyzes aldol condensations and acts via a mechanism similar to that of Nature’s aldolase enzymes [6]. Here we address the present status of antibody-catalyzed ester hydrolysis reactions and relate to some of the questions that are often raised in connection with this field.