Enzyme inhibitors ground-state analogs

This analysis reveals that enzymes bind the transition state more tightly than the ground state by a factor approximately equal to the rate of acceleration (ie, Kjs/Ks kuncaJkcat)- This method has been used to show, for example, that the peptide phos-phonate inhibitors of carboxypeptidase A are true transition state analogs. 

R. H. Abeles, Enzyme Inhibitors Ground State/ Transition-State Analogs , Drug, Dev. Res. 1987, 10, 221-234. 

In our context, an important class of reversible inhibitors are the transition state analogs [18], which are stable compounds designed to mimic the structure of an intermediate in the path of substrate s transformation by the enzyme. Such analogs are based in Pauling s postulate [19], which states that "an enzyme recognises and binds more tightly to the transition state than to the ground state of the substrate". 

Since binding interaction between an enzyme and a substrate is more favorable (>10 ) at the transition state than at the ground state, a transition state analog was expected to be a much better inhibitor than a substrate analog. Therefore, design of analogs of transition-state in the enzyme catalytic reaction was another popular field of research on PDHc inhibitors [54]. The normal enzyme-catalyzed pyruvate metabolic process is described in Scheme 1.13 [42]. 

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