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

doi:10.1021/ja201481j

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 journal › Article › peer-review

21 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 language	English
Pages (from-to)	7215-7221
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	133
Issue number	18
DOIs	https://doi.org/10.1021/ja201481j
Publication status	Published - May 11 2011
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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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.",

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AU - Sawada, Daisuke

AU - Tsukuda, Yuya

AU - Saito, Hiroshi

AU - Kakuda, Shinji

AU - Takimoto-Kamimura, Midori

AU - Ochiai, Eiji

AU - Takenouchi, Kazuya

AU - Kittaka, Atsushi

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

Abstract

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