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Samaja, G.A.; Castro, O.; Alvarez, L.D.; Dansey, M.V.; Escudero, D.S.; Veleiro, A.S.; Pecci, A.; Burton, G. "27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor" (2013) Bioorganic and Medicinal Chemistry Letters. 23(10):2893-2896
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Abstract:

27-Nor-Δ4-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20β-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- Δ4-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. © 2013 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
Autor:Samaja, G.A.; Castro, O.; Alvarez, L.D.; Dansey, M.V.; Escudero, D.S.; Veleiro, A.S.; Pecci, A.; Burton, G.
Filiación:Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina
IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina
IFIBYNE (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina
Palabras clave:DAF-12 receptor Caenorhabditis elegans daf-9 Mutants Dafachronic acid Molecular dynamics; 27 nor delta4 dafachronic acid; aldehyde; carboxylic acid derivative; cell nucleus receptor; cholesterol derivative; ligand; nuclear receptor DAF 12; unclassified drug; animal experiment; article; binding affinity; biological activity; Caenorhabditis elegans; controlled study; drug receptor binding; drug synthesis; in vitro study; in vivo study; ligand binding; molecular dynamics; molecular model; nonhuman; oxidative stress; phenotype; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cholestenes; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Ligands; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; Receptors, Cytoplasmic and Nuclear; Structure-Activity Relationship; Caenorhabditis elegans
Año:2013
Volumen:23
Número:10
Página de inicio:2893
Página de fin:2896
DOI: http://dx.doi.org/10.1016/j.bmcl.2013.03.071
Título revista:Bioorganic and Medicinal Chemistry Letters
Título revista abreviado:Bioorg. Med. Chem. Lett.
ISSN:0960894X
CODEN:BMCLE
CAS:Caenorhabditis elegans Proteins; Cholestenes; DAF-12 protein, C elegans; Ligands; Receptors, Cytoplasmic and Nuclear; delta4-dafachronic acid
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0960894X_v23_n10_p2893_Samaja

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Citas:

---------- APA ----------
Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., Pecci, A.,..., Burton, G. (2013) . 27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor. Bioorganic and Medicinal Chemistry Letters, 23(10), 2893-2896.
http://dx.doi.org/10.1016/j.bmcl.2013.03.071
---------- CHICAGO ----------
Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., et al. "27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor" . Bioorganic and Medicinal Chemistry Letters 23, no. 10 (2013) : 2893-2896.
http://dx.doi.org/10.1016/j.bmcl.2013.03.071
---------- MLA ----------
Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., et al. "27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor" . Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 10, 2013, pp. 2893-2896.
http://dx.doi.org/10.1016/j.bmcl.2013.03.071
---------- VANCOUVER ----------
Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., et al. 27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor. Bioorg. Med. Chem. Lett. 2013;23(10):2893-2896.
http://dx.doi.org/10.1016/j.bmcl.2013.03.071