The derivation of a potential transition state for the reduction reaction catalysed by 17[beta]-hydroxysteroid dehydrogenase--an approximate representation of its active site for use in drug design and discovery

In an effort to aid the drug discovery process, the approximate representation of the active site of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) has been derived from the consideration of the proposed mechanism for the reduction reaction. Using the transition-state (TS), the mode of action of a number of inhibitors has been rationalised. The results of the study suggest that the area of the active site corresponding to the C(17) area of the steroidal backbone is relatively constrained, as such, groups which possess large groups that are flexible in nature may possess a decreased inhibitory activity. The model is therefore a good start point for the development of novel inhibitors of 17beta-HSD and is a rapid technique for drug design and development.