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
-
Tetraspanins - Gateways for Infection
Infectious Disorders - Drug Targets Canine Nutritional Model: Influence of Age, Diet, and Genetics on Health and Well-Being
Current Nutrition & Food Science The Proteasome in Health and Disease
Current Pharmaceutical Design Bioinformatic Analysis of HIV-1 Entry and Pathogenesis
Current HIV Research Cellular Strategies to Combat Protein Misfolding: Intricate Role of Hsp70 in Stress Management
Current Chemical Biology The Role of Fibroblast Growth Factors in Tumor Growth
Current Cancer Drug Targets Port-a-Patch and Patchliner: High Fidelity Electrophysiology for Secondary Screening and Safety Pharmacology
Combinatorial Chemistry & High Throughput Screening Capsid (CA) Protein as a Novel Drug Target: Recent Progress in the Research of HIV-1 CA Inhibitors
Mini-Reviews in Medicinal Chemistry Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design Modulation of Nitric Oxide Pathway by Multiligands/RAGE Axis: A Crossing Point on the Road to Microvascular Complication in Diabetes
Current Enzyme Inhibition Is Combined Angiotensin-converting Enzyme Inhibition and Angiotensin Receptor Blockade Associated with Increased Risk of Cardiovascular Death in Hemodialysis Patients?
Current Hypertension Reviews GABA-A Receptor Complex and Memory Processes
Current Topics in Medicinal Chemistry Reactive Oxygen Species in Myocardial Reperfusion Injury: From Physiopathology to Therapeutic Approaches
Current Pharmaceutical Biotechnology Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 1: General Overview with a Focus on Ascorbic Acid
Inflammation & Allergy - Drug Targets (Discontinued) Behavioral Pharmacology of Cannabinoids with a Focus on Preclinical Models for Studying Reinforcing and Dependence-Producing Properties
Current Drug Abuse Reviews From Ontology-Based Gene Function to Physiological Model
Current Bioinformatics A Systematic Review of Drugs in Late-Stage Development for the Treatment of Multiple Sclerosis: A Focus on Oral Synthetic Drugs
Inflammation & Allergy - Drug Targets (Discontinued) Nanomedicinal Approach of Getting Across the Brood-Brain Barrier with Nanomedicinal Nanoparticles
Current Medicinal Chemistry The Tribbles-1 Protein in Humans: Roles and Functions in Health and Disease
Current Molecular Medicine Animal Models for Testing Anti-Prion Drugs
Current Topics in Medicinal Chemistry