Conversion of human-selective PPARalpha agonists to human/mouse dual agonists: a molecular modeling analysis
To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-ph...
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Published in | Bioorganic & medicinal chemistry letters Vol. 14; no. 24; pp. 6113 - 6116 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
20.12.2004
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Subjects | |
Online Access | Get full text |
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Summary: | To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARalpha leads to the species-specific divergence in ligand binding. Insights obtained in the molecular modeling studies of these key interactions resulted in the ability to convert a human-selective PPARalpha agonist to a human and mouse dual agonist within the same platform. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-894X |