Shokat K M, Leumann C J, Sugasawara R, Schultz P G
Department of Chemistry, University of California, Berkeley 94720.
Nature. 1989 Mar 16;338(6212):269-71. doi: 10.1038/338269a0.
The high binding affinity and specificity of antibodies for a wide range of ligands has recently been exploited in the generation of catalysts for acyl-transfer reactions, carbon-carbon bond forming and carbon-carbon bond cleaving reactions. In addition, a number of strategies are emerging for the generation of catalytic antibodies including transition state stabilization, catalysis by approximation, and the introduction of catalytic groups or cofactors into antibody combining sites. An important goal in the design of catalytic antibodies is the development of general rules relating hapten structure to the corresponding catalytic groups in the antibody combining site. We report here that electrostatic interactions between a hapten and the complementary antibody can be exploited to generate catalytic amino-acid side chains in an antibody-combining site. The antibody-catalysed reaction, a beta-elimination reaction, exhibits saturation kinetics, substrate specificity, competitive inhibition by hapten, and specific inactivation by a reagent that modifies carboxylate residues.
抗体对多种配体具有高结合亲和力和特异性，最近已被用于生成酰基转移反应、碳 - 碳键形成反应和碳 - 碳键裂解反应的催化剂。此外，出现了多种生成催化抗体的策略，包括过渡态稳定、近似催化以及将催化基团或辅因子引入抗体结合位点。催化抗体设计的一个重要目标是制定将半抗原结构与抗体结合位点中相应催化基团相关联的通用规则。我们在此报告，半抗原与互补抗体之间的静电相互作用可用于在抗体结合位点生成催化性氨基酸侧链。抗体催化的反应，即β - 消除反应，表现出饱和动力学、底物特异性、半抗原竞争性抑制以及被修饰羧酸盐残基的试剂特异性失活。
