Rational design of vitamin D3 analogues which selectively restore activity to a vitamin D receptor mutant associated with rickets
| Autor: | John T. Koh, Joel J. Bergh, Swann Sl, Mary C. Farach-Carson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vitamin
Models Molecular Transcriptional Activation medicine.medical_specialty Mutant Rickets Ligands Biochemistry Calcitriol receptor Cell Line chemistry.chemical_compound Transactivation Structure-Activity Relationship Internal medicine medicine Humans Physical and Theoretical Chemistry Cholecalciferol Chemistry Organic Chemistry Rational design medicine.disease Cell calcium Endocrinology Drug Design Mutation Receptors Calcitriol Calcium |
| Zdroj: | Organic letters. 4(22) |
| ISSN: | 1523-7060 |
| Popis: | [formula: see text] Vitamin D3-resistant rickets (VDRR) is associated with mutations to the Vitamin D receptor (VDR) which effect ligand-dependent transactivation. Some VDRR associated mutants directly disrupt ligand binding. Using the reported VDR-1,25-dihydroxy vitamin D3 (1,25(OH)2D3) cocrystal structure, three 1,25(OH)2D3 analogues were designed to uniquely complement the rickets associated mutant VDR(Arg274--Leu). The three analogues were 17 to 286 times more potent than 1,25(OH)2D3 with the mutant in cell-based assays and did not substantially activate cellular calcium influx. |
| Databáze: | OpenAIRE |
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