Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097
- Authors
- Huet, Tiphanie; Maehr, Hubert; Lee, Hong Jin; Uskokovic, Milan R.; Suh, Nanjoo; Moras, Dino; Rochel, Natacha
- Issue Date
- May-2011
- Publisher
- ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
- Citation
- MedChemComm, v.2, no.5, pp 424 - 429
- Pages
- 6
- Journal Title
- MedChemComm
- Volume
- 2
- Number
- 5
- Start Page
- 424
- End Page
- 429
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/21897
- DOI
- 10.1039/c1md00059d
- ISSN
- 2040-2503
2040-2511
- Abstract
- Derivatives of vitamin D3 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. © The Royal Society of Chemistry 2011.
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