New C15-Substituted Active Vitamin D-3

C15-Substituted 1 alpha,25-dihydroxyvitamin D-3 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...

Full description

Saved in:
Bibliographic Details
Published inOrganic letters Vol. 13; no. 11; pp. 2852 - 2855
Main Authors Shindo, Kanako, Kumagai, Go, Takano, Masashi, Sawada, Daisuke, Saito, Nozomi, Saito, Hiroshi, Kakuda, Shinji, Takagi, Ken-ichiro, Ochiai, Eiji, Horie, Kyohei, Takimoto-Kamimura, Midori, Ishizuka, Seiichi, Takenouchi, Kazuya, Kittaka, Atsushi
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 03.06.2011
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
SIDE-CHAINS
PALLADIUM
DESIGN
ANALOGS
1-ALPHA,25-DIHYDROXYVITAMIN-D-3
A-RING
RECEPTOR
DIFFERENTIATION
D-3
BINDING
Online AccessGet full text

Cover

More Information
Summary:C15-Substituted 1 alpha,25-dihydroxyvitamin D-3 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 angstrom 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.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol200828s