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Antibody‐Catalyzed Uni‐ and Multi‐Substrate Reactions Compared Using Transition‐State Binding ( K TS )
Author(s) -
Reymond JeanLouis,
Chen Yuanwei
Publication year - 1996
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.199600027
Subject(s) - chemistry , catalysis , hapten , dissociation constant , transition state , dissociation (chemistry) , catalytic efficiency , reaction rate constant , transition state analog , combinatorial chemistry , stereochemistry , computational chemistry , kinetics , antibody , organic chemistry , active site , quantum mechanics , biology , biochemistry , physics , receptor , immunology
Catalytic antibody technology is based on the equivalence between catalysis, transition‐state binding, and transition‐state analog binding. This simple concept has attracted enormous creativity to the field. Unfortunately a similar degree of simplicity is usually not evident in kinetic analyses of antibody‐catalyzed reactions. In particular, the rate enhancement k cat /k uncat does not allow one to compare reactions of different orders. Here we propose a simple language based on expressing K TS , the dissociation constant of the antibody‐transition‐state complex, together with a drawing for the corresponding transition‐state. The constant K TS was introduced by Kurz in 1963 as a quantitative expression for Pauling's formulation of catalysis. A small value of K TS describes tight transition‐state binding, and thus efficient catalysis. We show that this analysis allows a unified and remarkably simple description of antibody‐catalyzed reactions with very different levels of complexity. It also enforces a proper formulation of the “uncatalyzed” reaction, which has a critical influence in assessing catalytic efficiency. Comparing K TS with K i , the dissociation constant of the antibody‐hapten complex, shows how far binding to a designed hapten translates into catalysis.