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

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

Volume: 11 Issue: 7

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Loiodice F. and Pochetti G., Structural Insight Into the Crucial Role of Ligand Chirality in the Activation of PPARs by Crystallographic Methods, Current Topics in Medicinal Chemistry 2011; 11 (7) . https://dx.doi.org/10.2174/156802611795165106