Abstract
A majority of small molecule non-peptide ligands for chemokine receptors in general are characterized by the presence of one or two centrally located, positively charged nitrogen atoms and these compounds are also often of relatively similar elongated overall structure with terminal aromatic moieties. In the corresponding main ligand-binding crevice of the chemokine 7TM receptors is found a centrally located glutamic acid residue in position 6 of transmembrane segment VII in 74% of the chemokine receptors but only in approx. 1% of non-chemokine receptors. GluVII:06 has been demonstrated to be crucially important for the binding and action of a number of non-peptide ligands in for example the CCR1, CCR2 and CCR5 receptors. It is proposed that in chemokine receptors in general GluVII:06 serves as a selective anchor point for the centrally located, positively charged nitrogen of the small molecule ligands and that the two peripheral chemical moieties of the ligands from this central point in the receptor structure explore each of the two halves of the main ligand binding pocket. It is envisioned that knowledge of this binding mode can be exploited in structurebased discovery and design of novel chemokine receptor ligands and especially ligands with specifically optimized properties.
Keywords: 7-transmembrane (7TM) G-protein coupled receptors, chemokine receptor blockers, RS-504393, UCB-35625, YM-344031
Current Topics in Medicinal Chemistry
Title: GluVII:06 - A Highly Conserved and Selective Anchor Point for Non-Peptide Ligands in Chemokine Receptors
Volume: 6 Issue: 13
Author(s): Mette M. Rosenkilde and Thue W. Schwartz
Affiliation:
Keywords: 7-transmembrane (7TM) G-protein coupled receptors, chemokine receptor blockers, RS-504393, UCB-35625, YM-344031
Abstract: A majority of small molecule non-peptide ligands for chemokine receptors in general are characterized by the presence of one or two centrally located, positively charged nitrogen atoms and these compounds are also often of relatively similar elongated overall structure with terminal aromatic moieties. In the corresponding main ligand-binding crevice of the chemokine 7TM receptors is found a centrally located glutamic acid residue in position 6 of transmembrane segment VII in 74% of the chemokine receptors but only in approx. 1% of non-chemokine receptors. GluVII:06 has been demonstrated to be crucially important for the binding and action of a number of non-peptide ligands in for example the CCR1, CCR2 and CCR5 receptors. It is proposed that in chemokine receptors in general GluVII:06 serves as a selective anchor point for the centrally located, positively charged nitrogen of the small molecule ligands and that the two peripheral chemical moieties of the ligands from this central point in the receptor structure explore each of the two halves of the main ligand binding pocket. It is envisioned that knowledge of this binding mode can be exploited in structurebased discovery and design of novel chemokine receptor ligands and especially ligands with specifically optimized properties.
Export Options
About this article
Cite this article as:
Rosenkilde M. Mette and Schwartz W. Thue, GluVII:06 - A Highly Conserved and Selective Anchor Point for Non-Peptide Ligands in Chemokine Receptors, Current Topics in Medicinal Chemistry 2006; 6 (13) . https://dx.doi.org/10.2174/15680266106061319
DOI https://dx.doi.org/10.2174/15680266106061319 |
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
-
New Perspectives in Glioma Immunotherapy
Current Pharmaceutical Design Endocrine Disruptors and Human Health
Mini-Reviews in Medicinal Chemistry Toll-Like Receptors and their Role in Renal Pathologies
Inflammation & Allergy - Drug Targets (Discontinued) Clearance of Amyloid-β Peptide by Neuronal and Non-Neuronal Cells: Proteolytic Degradation by Secreted and Membrane associated Proteases
Current Neurovascular Research Aspects of Antisense Oligodeoxynucleotide, Ribozyme, DNA Enzyme and RNAi Design
Current Medicinal Chemistry - Central Nervous System Agents Comparative Anatomy, Physiology and In Vitro Models of the Blood-Brain and Blood-Retina Barrier
Current Medicinal Chemistry - Central Nervous System Agents Nanotechnology Advancements in the Diagnosis and Prevention of COVID-19: Past and Future
Coronaviruses Redox Homeostasis and Epigenetics in Non-alcoholic Fatty Liver Disease (NAFLD)
Current Pharmaceutical Design Triglycerides and Cardiovascular Risk
Current Cardiology Reviews Gene Therapy: How to Target the Kidney. Promises and Pitfalls
Current Gene Therapy The Management of Metastatic Bone Disease with the Combination of Bisphosphonates and Radiotherapy: From Theory to Clinical Practice
Anti-Cancer Agents in Medicinal Chemistry Antioxidant Therapy for Prevention of Inflammation, Ischemic Reperfusion Injuries and Allograft Rejection
Cardiovascular & Hematological Agents in Medicinal Chemistry Structure-Activity Relationship Studies: Methods and Ligand Design for G-Protein Coupled Peptide Receptors
Current Protein & Peptide Science Microparticles: From Biogenesis to Biomarkers and Diagnostic Tools in Cardiovascular Disease
Current Stem Cell Research & Therapy Waist-to-Hip Ratio (WHR) is Conversely Correlated to LAMP-2 Gene Expression Level: A Predictor for Lysosomal Lipid Entrance System
Current Nutrition & Food Science Neurochemical Substrates of MDMA Reward: Effects of the Inhibition of Serotonin Reuptake on the Acquisition and Reinstatement of MDMA-induced CPP
Current Pharmaceutical Design Nitric Oxide and Schizophrenia: Present Knowledge and Emerging Concepts of Therapy
CNS & Neurological Disorders - Drug Targets Pharmacological Characteristics of Parenteral IGF-I Administration
Current Pharmaceutical Biotechnology Dietary Toxins, Endoplasmic Reticulum (ER) Stress and Diabetes
Current Diabetes Reviews Metformin and Energy Metabolism in Breast Cancer: From Insulin Physiology to Tumour-initiating Stem Cells
Current Molecular Medicine