Stereospecificity, catalytic antibodies

Scheme 5.65. p-di ketone chemical trap hapten. Stereospecific aldol reaction catalyzed by the elicited catalytic antibodies Ab38C2 and Ab33F12. 

For the purposes of this treatise, the definition of asymmetric synthesis is a modification of that proposed by Morrison and Mosher [1] and as such will be applied to stereospecific reactions in which a prochiral unit in either an achiral or a chiral molecule is converted, by utility of other reagents and/or a catalytic antibody, into a chiral unit in such a manner that the stereoisomeric products are produced in an unequal manner. As such, the considerable body of work devoted to antibody-catalysis of stereoselective reactions including chiral resolutions, isomerizations and rearrangements are considered to be beyond the scope of this discussion. For information regarding these specific topics and more general information regarding the catalytic antibody field the following papers... 

In an alternative approach, Nakayama and Schultz [25] have successfully achieved the enantiofacial reduction of prochiral ketones. By utilizing the phosphonate hapten 15 catalytic antibodies were elicited which catalyze a highly stereospecific reduction of ketone 16 with sodium cyanoborohydride as a cofactor (Scheme 4). The most active antibody, A5, was found to have a pH optimum at acidic pH, consequently the reductions were performed in aqueous buffer at pH 5.0. The reaction was followed for multiple turnovers (>25) without any decrease in activity or stereoselectivity highlighting the utility of this catalytic system. 

Catalytic antibodies - These interesting molecules are antibodies with a very specific binding site to the transition state of an enzymatic reaction. The resulting molecules, called abzymes, act like antibodies. In some cases, abzymes can speed up reaction rates as much as lO -fold over the uncatalyzed reaction. The stereospecificity of enzymes (including abzymes) may provide a tremendous aid to the synthesis of stereospecific compounds in organic chemistry. 

The catalytic action of biocatalysts (enzymes, abzymes, antibodies, cells) is extremely efficient and selective compared to conventional chemical catalysts. They demonstrate higher reaction rates, milder reaction conditions and greater stereospecificity. Most of these properties come from the high molecular flexibility biocatalysts exhibit. On the other hand, this is also the origin of their major limit that holds back their application at the large scale, that is, the molecular stability, and then the catalyst lifetime. 

With at least partial understanding of essential features of enzymatic catalysis has come the desire to improve, by the modification of existing enzymes through genetic or chemical means to alter their substrate specificity without loss of catalytic efficiency, the field of protein engineering. A unique feature in the antibody design is that the stereospecific catalysis can be sought for reactions not known to be enzyme catalyzed. 

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