The 2α-(3-hydroxypropyl) group as an active motif in vitamin D3 analogues as agonists of the mutant vitamin D receptor (Arg274Leu)

Shinobu Honzawa; Yasuhiro Yamamoto; Atsushi Yamashita; Takayuki Sugiura; Masaaki Kurihara; Midori A. Arai; Shigeaki Kato; Atsushi Kittaka

doi:10.1016/j.bmc.2007.12.039

The 2α-(3-hydroxypropyl) group as an active motif in vitamin D₃ analogues as agonists of the mutant vitamin D receptor (Arg274Leu)

Shinobu Honzawa, Yasuhiro Yamamoto, Atsushi Yamashita, Takayuki Sugiura, Masaaki Kurihara, Midori A. Arai, Shigeaki Kato, Atsushi Kittaka

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

We designed and synthesized 1α- and 1β-hydroxymethyl-2α-(3-hydroxypropyl)-25-hydroxyvitamin D₃ (2a,b) and related analogues 2α-(3-hydroxypropyl)-25-hydroxyvitamin D₃ (3), Posner's analogues of 1α- and 1β-hydroxymethyl-25-hydroxyvitamin D₃ (4a,b), as well as 2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D₃ (5), to confirm the effect of the 1α-hydroxy group and/or 2α-(3-hydroxypropyl) group of vitamin D₃ analogues with the modified A-ring moiety on the mutant vitamin D receptor, VDR(Arg274Leu). The 2α-(3-hydroxypropyl) group showed better effect on enhancement of the transcriptional activity through the mutant VDR than the 1α- and 1β-hydroxymethyl groups.

Original language	English
Pages (from-to)	3002-3024
Number of pages	23
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	6
DOIs	https://doi.org/10.1016/j.bmc.2007.12.039
Publication status	Published - 2008 Mar 15
Externally published	Yes

Keywords

Mutant vitamin D receptor
Structure-function relationships
Vitamin D analogues
Vitamin D receptor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2007.12.039

Cite this

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title = "The 2α-(3-hydroxypropyl) group as an active motif in vitamin D3 analogues as agonists of the mutant vitamin D receptor (Arg274Leu)",

abstract = "We designed and synthesized 1α- and 1β-hydroxymethyl-2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (2a,b) and related analogues 2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (3), Posner's analogues of 1α- and 1β-hydroxymethyl-25-hydroxyvitamin D3 (4a,b), as well as 2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (5), to confirm the effect of the 1α-hydroxy group and/or 2α-(3-hydroxypropyl) group of vitamin D3 analogues with the modified A-ring moiety on the mutant vitamin D receptor, VDR(Arg274Leu). The 2α-(3-hydroxypropyl) group showed better effect on enhancement of the transcriptional activity through the mutant VDR than the 1α- and 1β-hydroxymethyl groups.",

keywords = "Mutant vitamin D receptor, Structure-function relationships, Vitamin D analogues, Vitamin D receptor",

author = "Shinobu Honzawa and Yasuhiro Yamamoto and Atsushi Yamashita and Takayuki Sugiura and Masaaki Kurihara and Arai, {Midori A.} and Shigeaki Kato and Atsushi Kittaka",

year = "2008",

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doi = "10.1016/j.bmc.2007.12.039",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry",

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T1 - The 2α-(3-hydroxypropyl) group as an active motif in vitamin D3 analogues as agonists of the mutant vitamin D receptor (Arg274Leu)

AU - Honzawa, Shinobu

AU - Yamamoto, Yasuhiro

AU - Yamashita, Atsushi

AU - Sugiura, Takayuki

AU - Kurihara, Masaaki

AU - Arai, Midori A.

AU - Kato, Shigeaki

AU - Kittaka, Atsushi

PY - 2008/3/15

Y1 - 2008/3/15

N2 - We designed and synthesized 1α- and 1β-hydroxymethyl-2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (2a,b) and related analogues 2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (3), Posner's analogues of 1α- and 1β-hydroxymethyl-25-hydroxyvitamin D3 (4a,b), as well as 2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (5), to confirm the effect of the 1α-hydroxy group and/or 2α-(3-hydroxypropyl) group of vitamin D3 analogues with the modified A-ring moiety on the mutant vitamin D receptor, VDR(Arg274Leu). The 2α-(3-hydroxypropyl) group showed better effect on enhancement of the transcriptional activity through the mutant VDR than the 1α- and 1β-hydroxymethyl groups.

AB - We designed and synthesized 1α- and 1β-hydroxymethyl-2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (2a,b) and related analogues 2α-(3-hydroxypropyl)-25-hydroxyvitamin D3 (3), Posner's analogues of 1α- and 1β-hydroxymethyl-25-hydroxyvitamin D3 (4a,b), as well as 2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (5), to confirm the effect of the 1α-hydroxy group and/or 2α-(3-hydroxypropyl) group of vitamin D3 analogues with the modified A-ring moiety on the mutant vitamin D receptor, VDR(Arg274Leu). The 2α-(3-hydroxypropyl) group showed better effect on enhancement of the transcriptional activity through the mutant VDR than the 1α- and 1β-hydroxymethyl groups.

KW - Mutant vitamin D receptor

KW - Structure-function relationships

KW - Vitamin D analogues

KW - Vitamin D receptor

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