Determining Inhibition Modality for Slow Binding Inhibitors

1 Potential Clincial Advantages of Slow Off-rate Inhibitors 

4 DETERMINING INHIBITION MODALITY FOR SLOW BINDING INHIBITORS 

As stated above, the vast majority of slow binding inhibitors that have been reported in the literature are active-site directed, hence competitive inhibitors. Nevertheless, there is no theoretical reason why noncompetitive or uncompetitive inhibitors could not also display slow binding behavior. Thus, to convert the apparent values of K, 

The inhibition modality for a slow binding inhibitor is easily determined from the effects of substrate concentration on the value of k0bs at any fixed inhibitor concentration (Tian and Tsou, 1982 Copeland, 2000). For a competitive inhibitor the value of fcobs will diminish hyperbolically with increasing substrate concentration according to Equation (6.15)  

For noncompetitive inhibition, the value of k bs will vary with substrate concentration in different way, depending on the value of a (see Chapter 3). When a = 1, kobs is independent of substrate concentration  

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Determining Inhibition Modality for Slow Binding Inhibitors 153... 

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