ANTIBODY-CATALYZED UNI-SUBSTRATE AND MULTI-SUBSTRATE REACTIONS COMPARED USING TRANSITION-STATE BINDING (K-TS)

Catalytic antibody technology is based on the equivalence between cata lysis, transition-state binding, and transition-state analog binding. This simple concept has attracted enormous creativity to the field. Un fortunately a similar degree of simplicity is usually not evident in k inetic analyses of antibody-catalyzed reactions. In particular, the ra te enhancement k(cat)/k(uncat), does not allow one to compare reaction s of different orders. Here we propose a simple language based on expr essing K-TS, the dissociation constant of the antibody-transition-stat e complex, together with a drawing for the corresponding transition-st ate. The constant K-TS was introduced by Kurz in 1963 as a quantitativ e expression for Pauling's formulation of catalysis. A small value of K-TS describes tight transition-state binding, and thus efficient cata lysis. We show that this analysis allows a unified and remarkably simp le description of antibody-catalyzed reactions with very different lev els of complexity. It also enforces a proper formulation of the ''unca talyzed'' reaction, which has a critical influence in assessing cataly tic efficiency. Comparing K-TS with K-i, the dissociation constant of the antibody-hapten complex, shows how far binding to a designed hapte n translates into catalysis.