C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands

The DAF-12 receptor in nematodes and the Liver X Receptor (LXR) in mammals are structurally related transcription factors that play key roles in determining the life span of the organism. Both types of receptors are activated by oxysterols, cholesterol metabolites with oxidized side chains. Restrict...

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Autores principales:	Del Fueyo, M.C., Dansey, M.V., Paolo, L.S., Pecci, A., Veleiro, A.S., Burton, G.
Formato:	JOUR
Materias:	DAF-12 receptor Dafachronic acid Liver X Receptor Oxocarbenium reduction Oxysterols 26 hydroxycholesterol bacterial protein cell nucleus receptor DAF 12 receptor DAF 12 receptor agonist diosgenin hormone receptor stimulating agent liver X receptor liver X receptor agonist unclassified drug cholestane derivative cholesterol derivative dafachronic acid oxysterol animal cell Article controlled study desilylation DNA binding heteronuclear single quantum coherence human human cell isomerization ligand binding mass spectrometry nonhuman nuclear magnetic resonance oxidation promoter region protein conformation reporter gene stereochemistry stereoisomerism transactivation transactivation assay agonists animal cell line chemical structure chemistry hamster HEK293 cell line metabolism nuclear magnetic resonance spectroscopy Animals Cell Line Cholestenes Cricetinae HEK293 Cells Humans Hydroxycholesterols Liver X Receptors Magnetic Resonance Spectroscopy Molecular Structure
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_0039128X_v112_n_p109_DelFueyo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_0039128X_v112_n_p109_DelFueyo
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spelling	todo:paper_0039128X_v112_n_p109_DelFueyo2023-10-03T14:49:18Z C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands Del Fueyo, M.C. Dansey, M.V. Paolo, L.S. Pecci, A. Veleiro, A.S. Burton, G. DAF-12 receptor Dafachronic acid Liver X Receptor Oxocarbenium reduction Oxysterols 26 hydroxycholesterol bacterial protein cell nucleus receptor DAF 12 receptor DAF 12 receptor agonist diosgenin hormone receptor stimulating agent liver X receptor liver X receptor agonist unclassified drug cholestane derivative cholesterol derivative dafachronic acid liver X receptor oxysterol animal cell Article controlled study desilylation DNA binding heteronuclear single quantum coherence human human cell isomerization ligand binding mass spectrometry nonhuman nuclear magnetic resonance oxidation promoter region protein conformation reporter gene stereochemistry stereoisomerism transactivation transactivation assay agonists animal cell line chemical structure chemistry hamster HEK293 cell line metabolism nuclear magnetic resonance spectroscopy Animals Cell Line Cholestenes Cricetinae HEK293 Cells Humans Hydroxycholesterols Liver X Receptors Magnetic Resonance Spectroscopy Molecular Structure Oxysterols The DAF-12 receptor in nematodes and the Liver X Receptor (LXR) in mammals are structurally related transcription factors that play key roles in determining the life span of the organism. Both types of receptors are activated by oxysterols, cholesterol metabolites with oxidized side chains. Restricting the movement of the oxysterol side chain to certain orientations may have profound effects in the activity profile, however this has not been explored so far. In a first attempt to obtain analogues of natural ligands of DAF-12 and LXR with restricted side chain mobility we introduced a 16,22-oxygen bridge in 26-hydroxycholesterol, a cholestenoic acid and a dafachronic acid (5-7). Diosgenin was used as starting material, the key step to obtain the 16,22 epoxy functionality was the one pot formation and reduction of a cyclic hemiketal via the oxocarbenium ion using sodium cyanoborohydride. All new compounds were characterized by NMR and mass spectrometry and assayed as ceDAF-12 or LXR ligands in transactivation cell-based assays. The dafachronic acid analogue 7 behaved as a ceDAF-12 agonist. © 2016 Elsevier Inc. All rights reserved. Fil:Dansey, M.V. 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:Veleiro, A.S. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0039128X_v112_n_p109_DelFueyo
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 Dafachronic acid Liver X Receptor Oxocarbenium reduction Oxysterols 26 hydroxycholesterol bacterial protein cell nucleus receptor DAF 12 receptor DAF 12 receptor agonist diosgenin hormone receptor stimulating agent liver X receptor liver X receptor agonist unclassified drug cholestane derivative cholesterol derivative dafachronic acid liver X receptor oxysterol animal cell Article controlled study desilylation DNA binding heteronuclear single quantum coherence human human cell isomerization ligand binding mass spectrometry nonhuman nuclear magnetic resonance oxidation promoter region protein conformation reporter gene stereochemistry stereoisomerism transactivation transactivation assay agonists animal cell line chemical structure chemistry hamster HEK293 cell line metabolism nuclear magnetic resonance spectroscopy Animals Cell Line Cholestenes Cricetinae HEK293 Cells Humans Hydroxycholesterols Liver X Receptors Magnetic Resonance Spectroscopy Molecular Structure Oxysterols
spellingShingle	DAF-12 receptor Dafachronic acid Liver X Receptor Oxocarbenium reduction Oxysterols 26 hydroxycholesterol bacterial protein cell nucleus receptor DAF 12 receptor DAF 12 receptor agonist diosgenin hormone receptor stimulating agent liver X receptor liver X receptor agonist unclassified drug cholestane derivative cholesterol derivative dafachronic acid liver X receptor oxysterol animal cell Article controlled study desilylation DNA binding heteronuclear single quantum coherence human human cell isomerization ligand binding mass spectrometry nonhuman nuclear magnetic resonance oxidation promoter region protein conformation reporter gene stereochemistry stereoisomerism transactivation transactivation assay agonists animal cell line chemical structure chemistry hamster HEK293 cell line metabolism nuclear magnetic resonance spectroscopy Animals Cell Line Cholestenes Cricetinae HEK293 Cells Humans Hydroxycholesterols Liver X Receptors Magnetic Resonance Spectroscopy Molecular Structure Oxysterols Del Fueyo, M.C. Dansey, M.V. Paolo, L.S. Pecci, A. Veleiro, A.S. Burton, G. C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
topic_facet	DAF-12 receptor Dafachronic acid Liver X Receptor Oxocarbenium reduction Oxysterols 26 hydroxycholesterol bacterial protein cell nucleus receptor DAF 12 receptor DAF 12 receptor agonist diosgenin hormone receptor stimulating agent liver X receptor liver X receptor agonist unclassified drug cholestane derivative cholesterol derivative dafachronic acid liver X receptor oxysterol animal cell Article controlled study desilylation DNA binding heteronuclear single quantum coherence human human cell isomerization ligand binding mass spectrometry nonhuman nuclear magnetic resonance oxidation promoter region protein conformation reporter gene stereochemistry stereoisomerism transactivation transactivation assay agonists animal cell line chemical structure chemistry hamster HEK293 cell line metabolism nuclear magnetic resonance spectroscopy Animals Cell Line Cholestenes Cricetinae HEK293 Cells Humans Hydroxycholesterols Liver X Receptors Magnetic Resonance Spectroscopy Molecular Structure Oxysterols
description	The DAF-12 receptor in nematodes and the Liver X Receptor (LXR) in mammals are structurally related transcription factors that play key roles in determining the life span of the organism. Both types of receptors are activated by oxysterols, cholesterol metabolites with oxidized side chains. Restricting the movement of the oxysterol side chain to certain orientations may have profound effects in the activity profile, however this has not been explored so far. In a first attempt to obtain analogues of natural ligands of DAF-12 and LXR with restricted side chain mobility we introduced a 16,22-oxygen bridge in 26-hydroxycholesterol, a cholestenoic acid and a dafachronic acid (5-7). Diosgenin was used as starting material, the key step to obtain the 16,22 epoxy functionality was the one pot formation and reduction of a cyclic hemiketal via the oxocarbenium ion using sodium cyanoborohydride. All new compounds were characterized by NMR and mass spectrometry and assayed as ceDAF-12 or LXR ligands in transactivation cell-based assays. The dafachronic acid analogue 7 behaved as a ceDAF-12 agonist. © 2016 Elsevier Inc. All rights reserved.
format	JOUR
author	Del Fueyo, M.C. Dansey, M.V. Paolo, L.S. Pecci, A. Veleiro, A.S. Burton, G.
author_facet	Del Fueyo, M.C. Dansey, M.V. Paolo, L.S. Pecci, A. Veleiro, A.S. Burton, G.
author_sort	Del Fueyo, M.C.
title	C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
title_short	C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
title_full	C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
title_fullStr	C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
title_full_unstemmed	C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands
title_sort	c(16)-c(22) oxygen-bridged analogues of cedaf-12 and lxr ligands
url	http://hdl.handle.net/20.500.12110/paper_0039128X_v112_n_p109_DelFueyo
work_keys_str_mv	AT delfueyomc c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT danseymv c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT paolols c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT peccia c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT veleiroas c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT burtong c16c22oxygenbridgedanaloguesofcedaf12andlxrligands
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C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands

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