Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants

Abstract

The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket.
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Dates and versions

hal-03766784 , version 1 (01-09-2022)

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Anna Belorusova, Daniela Rovito, Yassmine Chebaro, Stefanie Doms, Lieve Verlinden, et al.. Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants. International Journal of Molecular Sciences, 2022, 23 (15), pp.8445. ⟨10.3390/ijms23158445⟩. ⟨hal-03766784⟩
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