MECHANISM-BASED REPRESENTATION OF THE ACTIVE-SITE OF 5-ALPHA-REDUCTASE (5AR)

In the present study, we have attempted to determine a detailed repres entation of the 5 alpha-Reductase (5AR) active site involving the eluc idation of the transition state for the steroid Delta 4 reduction reac tion (the 'NADPH-substrate' complex), onto which steroidal and non-ste roidal inhibitors were superimposed. We conclude that : (i) there is a requirement for groups to mimic the steroid substrate A-ring; (ii) th e area about C(3), C(4), C(5) and C(6) of T appears to be sterically h indered, and; (iii) the area of the active site about the C(17) of the steroid substrate does not possess hydrogen bonding groups and is not restricted. (C) 1998 Elsevier Science Ltd. All rights reserved.