Structural evaluation of new 14-epimerized tachysterol analogs as hVDR agonists

我发现14-epi-19-去乙酰甾醇衍生物可以通过14次外聚得到。我成功地进行了它们的化学合成，并揭示了它们与天然速甾醇相比的显著稳定性，它们显示出了强大的VDR结合亲和力。此外，x射线共晶分析利用他们的配合物与人类VDR的配体结合域，令人惊讶的是，他们表现出前所未有的结合构型，c5,6 -s-反式和c7,8 -s-反式三烯构型，这是相反的天然维生素D3的c7,8 -烯构型。

I found that 14-epi-19-nortachysterol derivatives was able to be isolated by 14 epimerization. And I succeeded in their chemical synthesis and revealed their marked stability in comparison with natural tachysterol and they showed their potent VDR binding affinity. Also, X-ray co-crystallographic analyses were performed using their complex with the ligand binding domain of the human VDR, and surprisingly, they exhibited an unprecedented binding configurations, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of vitamin D3.