Abstract
Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore, chemokines and their receptors are excellent targets for developing drugs that are more specific and may be of benefit in the management of disease. Knowledge of the chemokine and chemokine receptor structures, and an understanding of the structural basis of their function are essential for structure-aided design of receptor decoys. Chemokine ligands bind their receptors with nanomolar (nM) affinity, and successful design of a small molecule antagonist should bind the receptor with similar high affinity and specificity. Chemokines bind receptors that belong to the 7-transmembrane class on leukocytes, and highly negatively charged proteoglycans that are present on the cell surface. Stru cture-function studies have identified regions in both the ligand and the receptor that mediate binding and activation. Structures of numerous chemokines have been solved though very little is known regarding receptor structures. This review will summarize the current knowledge on the structures, structure-function, and the efficacy of chemokine derivatives and functional domain peptides as antagonists, and discuss strategies for exploiting this information for designing decoys for inflammatory, autoimmune, and HIV-related diseases.
Keywords: chemokine, chemokine receptor, structure, drug design, receptor decoy, antagonist
Current Pharmaceutical Design
Title: Designing Decoys for Chemokine-Chemokine Receptor Interaction
Volume: 8 Issue: 24
Author(s): Krishna Rajarathnam
Affiliation:
Keywords: chemokine, chemokine receptor, structure, drug design, receptor decoy, antagonist
Abstract: Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore, chemokines and their receptors are excellent targets for developing drugs that are more specific and may be of benefit in the management of disease. Knowledge of the chemokine and chemokine receptor structures, and an understanding of the structural basis of their function are essential for structure-aided design of receptor decoys. Chemokine ligands bind their receptors with nanomolar (nM) affinity, and successful design of a small molecule antagonist should bind the receptor with similar high affinity and specificity. Chemokines bind receptors that belong to the 7-transmembrane class on leukocytes, and highly negatively charged proteoglycans that are present on the cell surface. Stru cture-function studies have identified regions in both the ligand and the receptor that mediate binding and activation. Structures of numerous chemokines have been solved though very little is known regarding receptor structures. This review will summarize the current knowledge on the structures, structure-function, and the efficacy of chemokine derivatives and functional domain peptides as antagonists, and discuss strategies for exploiting this information for designing decoys for inflammatory, autoimmune, and HIV-related diseases.
Export Options
About this article
Cite this article as:
Rajarathnam Krishna, Designing Decoys for Chemokine-Chemokine Receptor Interaction, Current Pharmaceutical Design 2002; 8 (24) . https://dx.doi.org/10.2174/1381612023393233
DOI https://dx.doi.org/10.2174/1381612023393233 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Discovery of 4-Aryl-4H-Chromenes as Potent Apoptosis Inducers Using a Cell- and Caspase-Based Anti-Cancer Screening Apoptosis Program (ASAP): SAR Studies and the Identification of Novel Vascular Disrupting Agents
Anti-Cancer Agents in Medicinal Chemistry Ethnopharmacological and Phytopharmaceutical Evaluation of Prosopis cineraria: An Overview and Future Prospects
Current Drug Metabolism Editorial (Thematic Issue: Linkage of Neurodegenerative Disorders with Other Health Issues – Volume II)
CNS & Neurological Disorders - Drug Targets In Vitro Models for the Study of Non-Alcoholic Fatty Liver Disease
Current Medicinal Chemistry A Single Fas Gene Mutation Changes Lupus Onset, Severity, Location, and Molecular Abnormalities in Mice
Current Molecular Medicine Advances in Analyses of Profens in Biological and Environmental Samples by Liquid Chromatography
Current Pharmaceutical Analysis Characterization and Management of Cutaneous Side Effects Related to the Immunosuppressive Treatment in Solid Organ Recipients
Current Drug Targets Immune Deviation Strategies in the Therapy of Psoriasis
Current Drug Targets - Inflammation & Allergy Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology Viral Infection and Obesity: Current Status and Future Prospective
Current Drug Metabolism Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants (ASIA) – Animal Models as a Proof of Concept
Current Medicinal Chemistry Immunoproteasome in Cancer and Neuropathologies: A New Therapeutic Target?
Current Pharmaceutical Design Outcome-Dependent Global Similarity Analysis of Imbalanced Core Signaling Pathways in Ischemic Mouse Hippocampus
CNS & Neurological Disorders - Drug Targets Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment
Current Topics in Medicinal Chemistry Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders
Current Drug Safety Attenuation of ERK/RSK2-Driven NFκB Gene Expression and Cancer Cell Proliferation by Kurarinone, a Lavandulyl Flavanone Isolated from Sophora flavescens Ait. Roots
Endocrine, Metabolic & Immune Disorders - Drug Targets Intraocular Inflammation and Systemic Immune-Mediated Diseases
Current Immunology Reviews (Discontinued) Biologic Therapy in Inflammatory Eye Conditions (Ophtalmology): Safety Profile
Current Drug Safety The Impetus of COVID -19 in Multiple Organ Affliction Apart from Respiratory Infection: Pathogenesis, Diagnostic Measures and Current Treatment Strategy
Infectious Disorders - Drug Targets 5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications
Current Medicinal Chemistry