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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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v112_n_p109_DelFueyo http://hdl.handle.net/20.500.12110/paper_0039128X_v112_n_p109_DelFueyo |
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paper:paper_0039128X_v112_n_p109_DelFueyo2023-06-08T15:03:11Z C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands Dansey, Maria Virginia Pecci, Adali Veleiro, Adriana Silvia Burton, Gerardo 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. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v112_n_p109_DelFueyo 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 Dansey, Maria Virginia Pecci, Adali Veleiro, Adriana Silvia Burton, Gerardo 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. |
| author |
Dansey, Maria Virginia Pecci, Adali Veleiro, Adriana Silvia Burton, Gerardo |
| author_facet |
Dansey, Maria Virginia Pecci, Adali Veleiro, Adriana Silvia Burton, Gerardo |
| author_sort |
Dansey, Maria Virginia |
| 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 |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v112_n_p109_DelFueyo http://hdl.handle.net/20.500.12110/paper_0039128X_v112_n_p109_DelFueyo |
| work_keys_str_mv |
AT danseymariavirginia c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT pecciadali c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT veleiroadrianasilvia c16c22oxygenbridgedanaloguesofcedaf12andlxrligands AT burtongerardo c16c22oxygenbridgedanaloguesofcedaf12andlxrligands |
| _version_ |
1768542979761373184 |