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

doi:10.1021/ol200828s

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	2852-2855
Number of pages	4
Journal	Organic Letters
Volume	13
Issue number	11
DOIs	https://doi.org/10.1021/ol200828s
Publication status	Published - Jun 3 2011
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/ol200828s

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title = "New C15-substituted active vitamin D3",

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 {\AA} 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.",

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

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doi = "10.1021/ol200828s",

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T1 - New C15-substituted active vitamin D3

AU - Shindo, Kanako

AU - Kumagai, Go

AU - Takano, Masashi

AU - Sawada, Daisuke

AU - Saito, Nozomi

AU - Saito, Hiroshi

AU - Kakuda, Shinji

AU - Takagi, Ken Ichiro

AU - Ochiai, Eiji

AU - Horie, Kyohei

AU - Takimoto-Kamimura, Midori

AU - Ishizuka, Seiichi

AU - Takenouchi, Kazuya

AU - Kittaka, Atsushi

PY - 2011/6/3

Y1 - 2011/6/3

N2 - 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.

AB - 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.

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DO - 10.1021/ol200828s

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JO - Organic Letters

JF - Organic Letters

IS - 11

ER -

New C15-substituted active vitamin D₃

Abstract

ASJC Scopus subject areas

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