Synthesis of 14-epi-2α-hydroxypropoxy-1α,25-dihydroxy-19- nortachysterol and its hVDR binding

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Recently, we evaluated a novel skeleton in the vitamin D family, 14-epi-1α,25(OH)2-19-nortachysterol, and discovered its unique binding configuration in the human vitamin D receptor (VDR) with the C5,6-and C7,8-s-trans triene configuration. Because of its unprecedented form, this skeleton has a promising characteristic profile for clinical use, and also the synthesis of its derivatives should be versatile. Therefore, we synthesized the novel analog, 2α-hydroxypropoxy substituted 14-epi-1α,25(OH) 2-19-nortachysterol, and evaluated its human VDR binding affinity. Although this substitution is one of the promising modification of vitamin D3 such as eldecalcitol (ED-71), it had negative effects on the binding affinity, and the compound showed lower affinity than 1α,25(OH)2D3 and its parent compound, 14-epi-1α,25(OH)2-19-nortachysterol. It was thought that the unprecedented binding configuration of this skeleton should not allow the terminal hydroxyl group of the 2α-substituent to construct effective hydrogen bond networks around the amino acid residues in the binding pocket.

Original languageEnglish
Pages (from-to)27-29
Number of pages3
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume136
Issue number1
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Calcitriol Receptors
Skeleton
Cholecalciferol
Vitamin D
Hydroxyl Radical
Hydrogen bonds
Substitution reactions
Derivatives
Amino Acids
Hydrogen
eldecalcitol
2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3

Keywords

  • 14-epi-19-Nortahcysterol
  • Binding affinity
  • Vitamin D analogs
  • Vitamin D receptor
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis of 14-epi-2α-hydroxypropoxy-1α,25-dihydroxy-19- nortachysterol and its hVDR binding. / Sawada, Daisuke; Tsukuda, Yuya; Saito, Hiroshi; Takagi, Kenichiro; Kakuda, Shinji; Takimoto-Kamimura, Midori; Ochiai, Eiji; Takenouchi, Kazuya; Kittaka, Atsushi.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 136, No. 1, 2013, p. 27-29.

Research output: Contribution to journalArticle

Sawada, D, Tsukuda, Y, Saito, H, Takagi, K, Kakuda, S, Takimoto-Kamimura, M, Ochiai, E, Takenouchi, K & Kittaka, A 2013, 'Synthesis of 14-epi-2α-hydroxypropoxy-1α,25-dihydroxy-19- nortachysterol and its hVDR binding', Journal of Steroid Biochemistry and Molecular Biology, vol. 136, no. 1, pp. 27-29. https://doi.org/10.1016/j.jsbmb.2012.11.014
Sawada, Daisuke ; Tsukuda, Yuya ; Saito, Hiroshi ; Takagi, Kenichiro ; Kakuda, Shinji ; Takimoto-Kamimura, Midori ; Ochiai, Eiji ; Takenouchi, Kazuya ; Kittaka, Atsushi. / Synthesis of 14-epi-2α-hydroxypropoxy-1α,25-dihydroxy-19- nortachysterol and its hVDR binding. In: Journal of Steroid Biochemistry and Molecular Biology. 2013 ; Vol. 136, No. 1. pp. 27-29.
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