New C15-substituted active vitamin D3

Kanako Shindo, Go Kumagai, Masashi Takano, Daisuke Sawada, Nozomi Saito, Hiroshi Saito, Shinji Kakuda, Ken Ichiro Takagi, Eiji Ochiai, Kyohei Horie, Midori Takimoto-Kamimura, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi Kittaka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

C15-Substituted 1α,25-dihydroxyvitamin D3 analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 Å shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.

Original languageEnglish
Pages (from-to)2852-2855
Number of pages4
JournalOrganic Letters
Volume13
Issue number11
DOIs
Publication statusPublished - Jun 3 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Shindo, K., Kumagai, G., Takano, M., Sawada, D., Saito, N., Saito, H., Kakuda, S., Takagi, K. I., Ochiai, E., Horie, K., Takimoto-Kamimura, M., Ishizuka, S., Takenouchi, K., & Kittaka, A. (2011). New C15-substituted active vitamin D3. Organic Letters, 13(11), 2852-2855. https://doi.org/10.1021/ol200828s