Download MendeleyStructure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.
Huet, T., Maehr, H., Lee, H.J., Uskokovic, M.R., Suh, N., Moras, D., Rochel, N.(2011) Medchemcomm 2: 424-429
- PubMed: 22180837
- DOI: https://doi.org/10.1039/C1MD00059D
- Primary Citation of Related Structures:
3O1D, 3O1E - PubMed Abstract:
Derivatives of vitamin D(3) containing a second side-chain emanating at C-20 are known as gemini and act as vitamin D receptor agonists. Recently, two of these, namely Gemini-0072 and the epimeric Gemini-0097, were selected for further studies in view of their high biological activities and lack of hypercalcemic effects. We now show that the two analogs recruit coactivator SRC-1 better than the parental gemini and act as VDR superagonists. The crystal structures of complexes of zVDR with Gemini-0072 and Gemini-0097 indicate that these ligands induce an extra cavity within the ligand-binding pocket similar to gemini and that their superagonistic activity is due to an increased stabilization of helix H12.
Organizational Affiliation:
D¨¦partement de Biologie et de G¨¦nomique Structurales, IGBMC (Institut de G¨¦n¨¦tique et de Biologie Mol¨¦culaire et Cellulaire), Centre National de la Recherche Scientifique, Institut National de la Sant¨¦ de la Recherche M¨¦edicale, Universit¨¦ de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
