title: Studies on the interaction between the vitamin D receptor and the radiolabelled 20-epi vitamin D analogue GS 1500.
abstract: Previous studies have shown that the binding affinity of a vitamin D analogue for the vitamin D receptor (VDR) does not correlate with the biological potency of the compound. In the present investigation the vitamin D analogue GS 1500, which is characterised by an altered stereochemistry at carbon C-20 (20-epi) and an aromatic ring in the side chain, was studied with respect to its interaction with the VDR. Using [3H]-GS 1500 as tracer, the receptor binding properties of GS 1500 were investigated and compared to those of 1,25(OH)2D3. The binding studies did not reveal a different binding site for GS 1500 than the one already established, and the binding affinity was in accordance with previously found values. At the level of VDR interaction with the vitamin D responsive element, GS 1500 did induce a binding complex at a lower concentration than 1,25(OH)2D3, which may help explain the difference in potency.
authors.affiliation: Department of Biochemistry, Leo Pharmaceutical Products, Ballerup, Denmark. ism@bio.cancer.dk
authors.forename: I S
authors.initials: IS
authors.lastname: Mathiasen
authors.forename: G
authors.initials: G
authors.lastname: Grue-Sørensen
authors.forename: C M
authors.initials: CM
authors.lastname: Hansen
authors.forename: L
authors.initials: L
authors.lastname: Binderup
authors.forename: F
authors.initials: F
authors.lastname: Björkling
mesh_terms: D000818:Animals; D011485:Protein Binding; D011869:Radioligand Assay; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013237:Stereoisomerism; D014316:Tritium; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D014316:Tritium; D014807:Vitamin D