Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor

Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Shinji Kakuda, Midori Takimoto-Kamimura, Eiji Ochiai, Kazuya Takenouchi, Atsushi Kittaka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In the study of the synthesis of 14-epi-19-norprevitamin D3, we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19- nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1α,25(OH)2D3.

Original languageEnglish
Pages (from-to)7215-7221
Number of pages7
JournalJournal of the American Chemical Society
Volume133
Issue number18
DOIs
Publication statusPublished - May 11 2011
Externally publishedYes

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Calcitriol Receptors
Vitamins
Derivatives
Isomerization
Ligands
previtamin D(3)

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor. / Sawada, Daisuke; Tsukuda, Yuya; Saito, Hiroshi; Kakuda, Shinji; Takimoto-Kamimura, Midori; Ochiai, Eiji; Takenouchi, Kazuya; Kittaka, Atsushi.

In: Journal of the American Chemical Society, Vol. 133, No. 18, 11.05.2011, p. 7215-7221.

Research output: Contribution to journalArticle

Sawada, D, Tsukuda, Y, Saito, H, Kakuda, S, Takimoto-Kamimura, M, Ochiai, E, Takenouchi, K & Kittaka, A 2011, 'Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor', Journal of the American Chemical Society, vol. 133, no. 18, pp. 7215-7221. https://doi.org/10.1021/ja201481j
Sawada, Daisuke ; Tsukuda, Yuya ; Saito, Hiroshi ; Kakuda, Shinji ; Takimoto-Kamimura, Midori ; Ochiai, Eiji ; Takenouchi, Kazuya ; Kittaka, Atsushi. / Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 18. pp. 7215-7221.
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