Conversion of human-selective PPARalpha agonists to human/mouse dual agonists: a molecular modeling analysis

Autor:	Yanping Xu, Mary K. Peters, Brian A. Oldham, Sarah B. Wilson, Aaron Kunkel, Allie Edward Tripp, Minmin Wang, Robert E. Babine, Leonard L. Winneroski, Richard W. Zink, Robert J. Ardecky, Deepa K. Rungta, Mccarthy James R, Garret J. Etgen, Christopher John Rito, D. R. Hutchison, Dawn A. Brooks, Dale E. Mais, Raymond F. Kauffman, Kathleen M. Ogilvie, Chahrzad Montrose-Rafizadeh
Rok vydání:	2004
Předmět:	Agonist Models Molecular Molecular model Pparα agonist Stereochemistry medicine.drug_class Carboxylic acid Clinical Biochemistry Pharmaceutical Science Ligands digestive system Biochemistry Chemical synthesis Mice Structure-Activity Relationship Species Specificity Drug Discovery medicine Structure–activity relationship Animals Humans PPAR alpha Binding site Molecular Biology chemistry.chemical_classification Molecular Structure Chemistry Organic Chemistry nutritional and metabolic diseases In vitro Cinnamates Drug Design Molecular Medicine lipids (amino acids peptides and proteins)
Zdroj:	Bioorganicmedicinal chemistry letters. 14(24)
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::538c575e3eaee66c93b66cea90fda590 https://pubmed.ncbi.nlm.nih.gov/15546740 Zobrazit plný text záznamu Full Text from ScienceDirect