Expanded Transition State Analogues

Abstract

Stable analogues of transition states are used as haptens to elicit antibodies that will catalyse the reaction under investigation. The present failure of such antibodies to equal the catalytic efficiency of enzymes has prompted a more detailed analysis of the structure of transition states. Calculations suggest that for many types of reaction, including the Diels-Alder reaction and addition-elimination reactions, interatomic distances in the transition state are longer than those in analogues hitherto used to elicit catalytic antibodies. Three possible solutions are proposed for the design and synthesis of stable analogues that match the longer interatomic distances of transition states: atom substitution, atom insertion and double atom insertion. Some applications of these ideas to specific reactions are described. The concept of expanded transition states is also valuable for associative processes as a way of avoiding product inhibition of the catalytic antibody; this is being explored for a phenylalanine transcarbamylase antibody.