27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor

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 norma...

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Autores principales:	Castro, Olga Alejandra, Alvarez, Lautaro Damián, Dansey, Maria Virginia, Veleiro, Adriana Silvia, Pecci, Adali, Burton, Gerardo
Publicado:	2013
Materias:	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 Proteins Cholestenes Dose-Response Relationship, Drug HEK293 Cells Humans Ligands Models, Molecular Molecular Conformation Molecular Dynamics Simulation Receptors, Cytoplasmic and Nuclear Structure-Activity Relationship
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0960894X_v23_n10_p2893_Samaja http://hdl.handle.net/20.500.12110/paper_0960894X_v23_n10_p2893_Samaja
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_0960894X_v23_n10_p2893_Samaja
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spelling	paper:paper_0960894X_v23_n10_p2893_Samaja2023-06-08T15:57:51Z 27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor Castro, Olga Alejandra Alvarez, Lautaro Damián Dansey, Maria Virginia Veleiro, Adriana Silvia Pecci, Adali Burton, Gerardo 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 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. Fil:Castro, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alvarez, L.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Dansey, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pecci, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0960894X_v23_n10_p2893_Samaja http://hdl.handle.net/20.500.12110/paper_0960894X_v23_n10_p2893_Samaja
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Castro, Olga Alejandra Alvarez, Lautaro Damián Dansey, Maria Virginia Veleiro, Adriana Silvia Pecci, Adali Burton, Gerardo 27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
topic_facet	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
description	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.
author	Castro, Olga Alejandra Alvarez, Lautaro Damián Dansey, Maria Virginia Veleiro, Adriana Silvia Pecci, Adali Burton, Gerardo
author_facet	Castro, Olga Alejandra Alvarez, Lautaro Damián Dansey, Maria Virginia Veleiro, Adriana Silvia Pecci, Adali Burton, Gerardo
author_sort	Castro, Olga Alejandra
title	27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
title_short	27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
title_full	27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
title_fullStr	27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
title_full_unstemmed	27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor
title_sort	27-nor-δ4-dafachronic acid is a synthetic ligand of caenorhabditis elegans daf-12 receptor
publishDate	2013
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0960894X_v23_n10_p2893_Samaja http://hdl.handle.net/20.500.12110/paper_0960894X_v23_n10_p2893_Samaja
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27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor

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