Biological evaluation and synthesis of calcitroic acid.

ABSTRACT: We describe the synthesis and broad profiling of calcitroic acid (CTA) as vitamin D receptor (VDR) ligand. The x-ray co-crystal structure of the Danio Rerio VDR ligand binding domain in complex with CTA and peptide MED1 confirmed an agonistic conformation of the receptor. CTA adopted a similar conformation as 1,25(OH)₂D₃ in the binding pocket. A hydrogen bond with His333 and a water molecule were observed in the binding pocket, which was accommodated due to the shorter CTA side chain. In contrast, 1,25(OH)₂D₃ interacted with His423 and His333 due to its longer side chain. In vitro, the EC₅₀ values of CTA and CTA-ME for VDR-mediated transcription were 2.89 µM and 0.66 µM, respectively, confirming both compounds as VDR agonists. CTA was

SUBMITTER: Yu OB 

PROVIDER: S-EPMC8592288 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature