ANTI-METALLOCENE ANTIBODIES - A NEW APPROACH TO ENANTIOSELECTIVE CATALYSIS OF THE DIELS-ALDER REACTION

被引:96
作者
YLIKAUHALUOMA, JT
ASHLEY, JA
LO, CH
TUCKER, L
WOLFE, MM
JANDA, KD
机构
[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
[2] Scripps Res Inst, DEPT CHEM, LA JOLLA, CA 92037 USA
关键词
D O I
10.1021/ja00132a001
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We have shown how a constrained bicyclo[2.2.2]octene hapten can elicit antibody catalysts for the Diels-Alder reaction between 4-carboxybenzyl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide (Gouverneur, V. E,; de Pascual-Teresa, B.; Beno, B.; Janda, K. D.; Lerner, R. A. Science 1993, 262, 204). In the present study we have developed a new approach to hapten design for elicitation of Diels-Alder catalytic antibodies. Our strategy was to engage the freely rotating eta(5)-cyclopentadienyl iron complex as the haptenic group. By applying such a flexible hapten we set out to determine if the immune system could freeze out a conformer which mimics the Diels-Alder transition state and hence produce new Diels-Alderases. If so, how would the catalytic rates, diastereo- and enantioselectivity of these antibodies compare with those of antibodies elicited by the former methodology? We generated antibodies that catalyzed the Diels-Alder reaction with high enantio- and diastereoselectivity and had effective molarities (EM) comparable to those of antibodies elicited using the constrained bicyclo[2.2.2]octene haptens. This methodology offers a new approach to the production of antibodies for the catalysis of other reactions with pericyclic, highly-ordered transition states.
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页码:7041 / 7047
页数:7
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