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 journalArticlepeer-review

19 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 languageEnglish
Pages (from-to)3002-3024
Number of pages23
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number6
DOIs
Publication statusPublished - 2008 Mar 15
Externally publishedYes

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

Fingerprint Dive into the research topics of 'The 2α-(3-hydroxypropyl) group as an active motif in vitamin D<sub>3</sub> analogues as agonists of the mutant vitamin D receptor (Arg274Leu)'. Together they form a unique fingerprint.

Cite this