Structural Insight Into the Crucial Role of Ligand Chirality in the Activation of PPARs by Crystallographic Methods

Author(s): F. Loiodice, G. Pochetti

Journal Name: Current Topics in Medicinal Chemistry

Volume 11 , Issue 7 , 2011

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Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular disease, obesity, and diabetes. These receptors show a high degree of stereoselectivity towards several classes of drugs. This review provides an overview of most papers reporting the influence of stereochemistry on PPAR activation. Some cases in which chirality is a crucial point in determining the PPAR binding mode are reviewed and discussed with the aim to show how enantiomeric recognition originates at the molecular level. The structural characterization by crystallographic methods of complexes formed by PPARs with their ligands turns out to be an essential tool to explain receptor stereoselectivity.

Keywords: Chirality, stereoselectivity, peroxisome proliferator-activated receptors, crystallographic methods, selective modulators, nuclear receptors, thiazolidinediones, fibrates, transcription factors, cardiovascular disease, obesity, diabetes, tereoselectivity, PPAR activation, complexes

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Article Details

Year: 2011
Page: [819 - 839]
Pages: 21
DOI: 10.2174/156802611795165106
Price: $65

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