National Center for
3AUR: Crystal Structure Of The Human Vitamin D Receptor Ligand Binding Domain Complexed With Yne-diene Type Analog Of Active 14-epi-2beta- Methyl-19-norvitamin D3
Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor
J. Am. Chem. Soc. (2011) 133 p.7215-7221
In the study of the synthesis of 14-epi-19-norprevitamin D(3), we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1alpha,25(OH)(2)D(3).