27-Nor-Δ(4)-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor.
Bioorg Med Chem Lett
; 23(10): 2893-6, 2013 May 15.
Article
em En
| MEDLINE
| ID: mdl-23570785
ABSTRACT
27-Nor-Δ(4)-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20ß-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants and restored their normal resistance to oxidative stress. 27-Nor-Δ(4)-dafachronic acid was also able to directly bind and activate DAF-12 in a transactivation cell-based luciferase reporter assay, although it was less active than the corresponding 25R-and 25S dafachronic acids. The binding mode of the 27-Nor steroid was studied by molecular dynamics using a homology model of the CeDAF-12 receptor.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colestenos
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Caenorhabditis elegans
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Receptores Citoplasmáticos e Nucleares
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Proteínas de Caenorhabditis elegans
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article