Catalytic Antibodies

Abstract

Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved as enzymic catalysts with the appropriate substrates. These substrates are distinguished by the structural congruence of both hydrolysis products with haptenic fragments. The haptens were potent inhibitors of this esterolytic activity, in agreement with their classification as transition state analogs. Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. These studies indicate a potentially general approach to catalyst design.

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

“…Since the original discovery of catalytic antibodies (30)(31)(32), ample data established their contribution to pathological effects in disease (33) as well as their possible biomedical applications (23,34). It was shown that elevated levels of the autoantibody catalytic activity correlated with an autoimmune response in human and mice models (16,21,35).…”

Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled “Nanozyme”

“…[1][2][3][4] The extraordinary efficiency of enzymes under mild physiological conditions has challenged chemists to design enzyme mimics with the goals of achieving useful catalytic processes and furthering our understanding of enzymes. To emulate this mode of catalysis, many research groups have designed synthetic hosts capable of binding and directing the reactivity of guest molecules.…”

“…General reaction scheme of the 3-aza Cope rearrangement. Starting from a propargyl enammonium cation, [3,3] sigmatropic rearrangement leads to an allenyl iminium cation, which then hydrolyzes to an allenyl aldehyde.…”

Molecular Evolution of Catalytic Antibodies in Autoimmune Mice

“…Phosphonate derivatives were the first and most successful haptens to elicit tailor-made esterolytic catAbs. They show good approximation of the transition state of substrates for ester hydrolysis because of their tetrahedral geometry and anionic character (3,4). Since then, a variety of catAbs has been generated based on haptenic TSAs (5).…”