STUDIES ON THE INTERACTION BETWEEN THE VITAMIN-D-RECEPTOR AND THE RADIOLABELED 20-EPI VITAMIN-D ANALOG GS-1500

Previous studies have shown that the binding affinity of a vitamin D a nalogue for the vitamin D receptor (VDR) does not correlate with the b iological potency of the compound. In the present investigation the vi tamin D analogue GS 1500, which is characterised by an altered stereoc hemistry at carbon C-20 (20-epi) and an aromatic ring in the side chai n, was studied with respect to its interaction with the VDR. Using [H- 3]-GS 1500 as tracer, the receptor binding properties of GS 1500 were investigated and compared to those of 1,25(OH)(2)D-3. The binding stud ies did not reveal a different binding site for GS 1500 than the one a lready established, and the binding affinity was in accordance with pr eviously found values. At the level of VDR interaction with the vitami n D responsive element, GS 1500 did induce a binding complex at a lowe r concentration than 1,25(OH)(2)D-3, which may help explain the differ ence in potency. (C) 1998 Academic Press.