UMYMFOR   05516
UNIDAD DE MICROANALISIS Y METODOS FISICOS EN QUIMICA ORGANICA
Unidad Ejecutora - UE
artículos
Título:
27-Nor-delta4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
Autor/es:
SAMAJA, GISELA; CASTRO, OLGA; ALVAREZ, LAUTARO D.; DANSEY, MARIA V.; ESCUDERO, DAIANA S.; VELEIRO, ADRIANA S.; PECCI, ADALI; BURTON, GERARDO
Revista:
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 23 p. 2893 - 2896
ISSN:
0960-894X
Resumen:
27-Nor-D4-dafachronic acid was prepared in 9 steps and 14 % overall yield by two sequential 2-carbon homologations from 20b-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50)C. elegans  mutants and restored their normal resistance to oxidative stress. 27-nor-D4-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.