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
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
![](/images/wayfinder.jpg)
- 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
-
Potential Advantages of Using Synchrotron X-ray Based Techniques in Pediatric Research
Current Medicinal Chemistry Renal and Urological Diseases of the Newborn Neonatal Acute Kidney Injury
Current Pediatric Reviews An Overall Picture of Chemokine Receptors: Basic Research and Drug Development
Current Pharmaceutical Design Contribution of Transcriptome to Elucidate the Biology of Plasmodium spp
Current Topics in Medicinal Chemistry Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants (ASIA) – Animal Models as a Proof of Concept
Current Medicinal Chemistry Intricate Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Isoforms in Normal Physiology and Disease
Current Molecular Medicine Phytosomes as Biocompatible Carriers of Natural Drugs
Current Medicinal Chemistry Physiological Effect and Therapeutic Application of Alpha Lipoic Acid
Current Medicinal Chemistry The Development of Cannabinoid CBII Receptor Agonists for the Treatment of Central Neuropathies
Central Nervous System Agents in Medicinal Chemistry Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy
Current Vascular Pharmacology Oxidative Stress, Endothelial Dysfunction and Atherosclerosis
Current Pharmaceutical Design Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses
Current Topics in Medicinal Chemistry Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 2: Calciferol and the Significance of Nutrient Supplements
Inflammation & Allergy - Drug Targets (Discontinued) Novel Therapeutic Strategies in Major Depression: Focus on RNAi and Ketamine
Current Pharmaceutical Design The Potential and Limitations of p38MAPK as a Drug Target for the Treatment of Hematological Malignancies
Current Drug Targets Interaction between Microbes and Host Intestinal Health: Modulation by Dietary Nutrients and Gut-Brain-Endocrine-Immune Axis
Current Protein & Peptide Science Possible Role of the Extracellular Signal-Regulated Kinase (ERK) in Reward-Controlled Learning and Addiction
Current Neuropharmacology Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia
Current Gene Therapy Endocannabinoid System: A Multi-Facet Therapeutic Target
Current Clinical Pharmacology Caveolae’s Behavior in Norm and Pathology
New Emirates Medical Journal