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.
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
Current Topics in Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/156802611795165106 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Intravascular Ultrasound to Guide Drug-Eluting Stents Implantation
Cardiovascular & Hematological Agents in Medicinal Chemistry Atherosclerotic and Non-Atherosclerotic Coronary Heart Disease in Women
Current Medicinal Chemistry Regulatory T Cells and Tolerogenic Dendritic Cells as Critical Immune Modulators in Atherogenesis
Current Pharmaceutical Design Can Group Exercise Programs Improve Health Outcomes in Pregnant Women? A Systematic Review
Current Women`s Health Reviews Recent Clinical Aspects of Hyperprolactinemia Induced by Antipsychotics
Reviews on Recent Clinical Trials Serum Specific Vasopressin-Degrading Activity is Related to Blood Total Cholesterol Levels in Men but not in Women
Medicinal Chemistry Pathophysiology and Treatment of Obesity Hypertension
Current Pharmaceutical Design Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and LDL Lowering in the Contemporary Management of Dyslipidemia
Cardiovascular & Hematological Agents in Medicinal Chemistry New and Promising Chemotherapeutics for Emerging Infections Involving Drug-resistant Non-albicans Candida Species
Current Topics in Medicinal Chemistry Drug Delivery Systems for the Treatment of Diabetes Mellitus: State of the Art
Current Pharmaceutical Design Obesity, Metabolic Syndrome and the Risk of Microvascular Complications in Patients with Diabetes mellitus
Current Pharmaceutical Design Immunotherapeutic Approaches in MS: Update on Pathophysiology and Emerging Agents or Strategies 2006
Endocrine, Metabolic & Immune Disorders - Drug Targets Mitochondrial MMP Activation, Dysfunction and Arrhythmogenesis in Hyperhomocysteinemia
Current Vascular Pharmacology Perinatal and Neonatal Outcomes of Lithium-Treated and Untreated Bipolar Women During Pregnancy: A Review of Present Literature
Current Psychopharmacology Bioprocess and Bioreactor: Next Generation Technology for Production of Potential Plant-based Antidiabetic and Antioxidant Molecules
Current Medicinal Chemistry Inhibitory Smad7: Emerging Roles in Health and Disease
Current Molecular Pharmacology Acute Cystitis Caused by Commensal Neisseria oralis: A Case Report and Review of the Literature
Infectious Disorders - Drug Targets Exosome Limitations in the Treatment of Inflammatory Diseases
Current Pharmaceutical Design Pancreatic Cancer in Obesity: Epidemiology, Clinical Observations, and Basic Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance
Infectious Disorders - Drug Targets