Pergamon SUBSTRATE-SELECT IVE MECHANISMS IN B IOCATALYS IS DEMONSTRATED WITH A VERSATILE AND EFF IC IENT ALDOLASE ANTIBODY

Abstract: A structure-activity relationship study with a series of aldol substrates shows that the mechanism of the antibody 38C2-catalyzed retrograde aldol reaction depends on the nature of the substrate With electron-deficient substrates an early deprotonation precedes the C-C bond cleavage while with electron-rich substrates the catalytic mechanism involves an initial C-C bond cleavage leading to a positively charged intermediate. © 1999 Elsevier Science Ltd. All rights reserved. The importance of the aldol condensation reaction stems not only from the key role it plays in biosynthesis but also from the fact that this reaction represents one of the main carbon-carbon bond forming methodologies in organic hemistry. 1 The aldol condensation is a non-trivial multistep reaction that is catalyzed by either bases or acids as well as by metals. Mechanistic studies of biocatalyzed aldol reactions are useful because they can teach us how to design efficient synthetic aldol catalysts. Studies of substituent effects could be particularly beneficial for this purpose, as they provide important information about charge development in the transition state. 2 However, since the natural aldolase nzymes are highly substrate specific, the use of a broad range of substrates toobtain linear free-energy relationships is difficult or impossible. Fortunately, this problem has been recently removed with the report on the antibody aldolases, such as 38C2 and 33F12. 3These antibodies, which were obtained via the reactive immunization technique, exhibit hig