Alcohol Dehydrogenase Structure-Activity Relationships

Abstract

Substituent constants and regression analysis have been employed in a study of the structure-activity relationship of binding and inhibition of alcohol dehydrogenase with small molecules. Using this technique, it is possible to separate the hydrophobic, electronic, and steric roles of substituents in the interaction of the small molecules with the enzyme. It is shown that electron-withdrawing substituents decrease interaction of amides and alcohols. Substituents on the α carbon atom of amides and acids do not show a steric effect. From these two facts it is concluded that the carbonyl function attaches to the enzyme via the oxygen atom rather than the carbon atom. The dependence of interaction on the hydrophobic character of the substituents is found to be similar to that of many other sets of congeners acting on simple proteins and enzymes. Although there is some evidence that interaction is related parabolically to lipophilic character of the organic compounds, insufficient results are in hand to define sharply the relationship. The results of this study show that data from different laboratories using different types of compounds can be quantitatively compared and from such comparisons a self-consistent picture emerges.