TY - JOUR
T1 - Effects of 2-substitution on 14-
T2 - Epi -19-nortachysterol-mediated biological events: Based on synthesis and X-ray co-crystallographic analysis with the human vitamin D receptor
AU - Sawada, Daisuke
AU - Kakuda, Shinji
AU - Takeuchi, Akiko
AU - Kawagoe, Fumihiro
AU - Takimoto-Kamimura, Midori
AU - Kittaka, Atsushi
N1 - Funding Information:
This work was supported in part by Grants-in-Aid from the Japan Society for the Promotion of Science (no. 23590015 to D. S.; no. 24590021 and 15K07869 to A. K.), the Uehara Memorial Foundation, and Takeda Science Foundation (to D. S.). The authors are grateful to AMED-CREST, AMED (JP17gm0710007h0104) for partial support in the preparation of this manuscript.
Publisher Copyright:
© The Royal Society of Chemistry 2018.
PY - 2018
Y1 - 2018
N2 - Both 2α- and 2β-hydroxypropyl substituted 14-epi-1α,25-dihydroxy-19-nortachysterols were synthesized to study the human vitamin D receptor (hVDR) binding affinity, binding configurations, and interactions with amino acid residues in the ligand binding domain of hVDR by X-ray co-crystallographic analysis. In conjunction with our previous results on 14-epi-19-nortachysterol, 2-methylidene-, 2α-methyl-, 2β-methyl, and 2α-hydroxypropoxy-14-epi-19-nortachysterol, we propose a variety of effects of substitution at the C2 position in the 14-epi-19-nortachysterol skeleton on biological activities.
AB - Both 2α- and 2β-hydroxypropyl substituted 14-epi-1α,25-dihydroxy-19-nortachysterols were synthesized to study the human vitamin D receptor (hVDR) binding affinity, binding configurations, and interactions with amino acid residues in the ligand binding domain of hVDR by X-ray co-crystallographic analysis. In conjunction with our previous results on 14-epi-19-nortachysterol, 2-methylidene-, 2α-methyl-, 2β-methyl, and 2α-hydroxypropoxy-14-epi-19-nortachysterol, we propose a variety of effects of substitution at the C2 position in the 14-epi-19-nortachysterol skeleton on biological activities.
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U2 - 10.1039/c8ob00158h
DO - 10.1039/c8ob00158h
M3 - Article
C2 - 29560490
AN - SCOPUS:85044989840
SN - 1477-0520
VL - 16
SP - 2448
EP - 2455
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 14
ER -