Abstract
Human interleukin 5 (IL5) is the major hematopoietin that stimulates the proliferation, migration and activation of eosinophils and is implicated in the pathogenesis of inflammatory and other myeloproliferative diseases. IL5 functions through the signaling of a common receptor subunit β (βc), in a receptor activation process that requires initial recruitment of an IL5 specific receptor subunit α (IL5Rα), for cytokine presentation to βc. Important advances have been made to understand molecular mechanisms of cytokine recognition and receptor antagonism. Mutational studies indicate that a pair of charge complementary regions play an essential role in specific interaction between IL5Rα and IL5. Moreover, peptide studies with the IL5 system have identified a cyclic peptide inhibitor, AF17121, which binds specifically to IL5Rα by mimicking the cytokine. A key receptor-recognition pharmacophore has been identified in this peptide inhibitor, and sites of inhibitor recognition can be proposed in the homology-deduced structural model of IL5Rα. These results provide an experimental platform to derive enhanced-potency peptidomimetic inhibitors. Such inhibitors have potential use as tools to evaluate the role of eosinophilia in disease and as potential leads to antagonists to treat hyper-eosinophilic diseases such as eosinophilic esophagitis, asthma and chronic myeloproliferative leukemias.
Current Pharmaceutical Design
Title: Structure-Based Rationale for Interleukin 5 Receptor Antagonism
Volume: 14 Issue: 12
Author(s): Tetsuya Ishino, Adrian E. Harrington, Hosahudya Gopi and Irwin Chaiken
Affiliation:
Abstract: Human interleukin 5 (IL5) is the major hematopoietin that stimulates the proliferation, migration and activation of eosinophils and is implicated in the pathogenesis of inflammatory and other myeloproliferative diseases. IL5 functions through the signaling of a common receptor subunit β (βc), in a receptor activation process that requires initial recruitment of an IL5 specific receptor subunit α (IL5Rα), for cytokine presentation to βc. Important advances have been made to understand molecular mechanisms of cytokine recognition and receptor antagonism. Mutational studies indicate that a pair of charge complementary regions play an essential role in specific interaction between IL5Rα and IL5. Moreover, peptide studies with the IL5 system have identified a cyclic peptide inhibitor, AF17121, which binds specifically to IL5Rα by mimicking the cytokine. A key receptor-recognition pharmacophore has been identified in this peptide inhibitor, and sites of inhibitor recognition can be proposed in the homology-deduced structural model of IL5Rα. These results provide an experimental platform to derive enhanced-potency peptidomimetic inhibitors. Such inhibitors have potential use as tools to evaluate the role of eosinophilia in disease and as potential leads to antagonists to treat hyper-eosinophilic diseases such as eosinophilic esophagitis, asthma and chronic myeloproliferative leukemias.
Export Options
About this article
Cite this article as:
Ishino Tetsuya, Harrington E. Adrian, Gopi Hosahudya and Chaiken Irwin, Structure-Based Rationale for Interleukin 5 Receptor Antagonism, Current Pharmaceutical Design 2008; 14 (12) . https://dx.doi.org/10.2174/138161208784246144
DOI https://dx.doi.org/10.2174/138161208784246144 |
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
-
Editorial
Current Respiratory Medicine Reviews Chronic Obstructive Pulmonary Disease and Oxidative Stress
Current Pharmaceutical Biotechnology Effectiveness of Long-Term Macrolide Therapy in Cryptogenic Organising Pneumonia
Current Respiratory Medicine Reviews Acitretin Loaded Nanocarrier Gel: Formulation and Exploration of <i>In-vitro</i> Release Kinetics
Current Nanomedicine Human Exposure to Endocrine Disruptors and Breast Milk
Endocrine, Metabolic & Immune Disorders - Drug Targets Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Hymenoptera Venom Proteins and Peptides for Diagnosis and Treatment of Venom Allergic Patients
Inflammation & Allergy - Drug Targets (Discontinued) Editorial [Hot Topic Advantages and Disadvantages of Inhaled Corticosteroids in the Treatment of Pulmonary Diseases Guest Editor: Nazan Cobanoglu]
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Respiratory Syncytial Virus and Asthma in Twin Children: Lessons from the Population-Based Danish Registries
Current Respiratory Medicine Reviews Information Management for the Study of Allergies
Inflammation & Allergy - Drug Targets (Discontinued) Sublingual Allergen Immunotherapy: Immunological Mechanisms and Prospects for Refined Vaccine Preparations
Current Medicinal Chemistry Therapeutic Benefit and Biological Importance of Ginkgetin in the Medicine: Medicinal Importance, Pharmacological Activities and Analytical Aspects
Current Bioactive Compounds Probiotics and Oral Health
Current Pharmaceutical Design Emerging Cytokines in Allergic Airway Inflammation: A Genetic Update
Current Immunology Reviews (Discontinued) Editorial
Inflammation & Allergy - Drug Targets (Discontinued) Targeting the Human Thioredoxin System by Diverse Strategies to Treat Cancer and Other Pathologies
Recent Patents on DNA & Gene Sequences CD147 Interacts with NDUFS6 in Regulating Mitochondrial Complex I Activity and the Mitochondrial Apoptotic Pathway in Human Malignant Melanoma Cells
Current Molecular Medicine Prospects of Gene Therapy for Pulmonary Diseases: Progress and Limitations
Medicinal Chemistry Age-Related Pharmacokinetic and Pharmacodynamic Changes and Related Risk of Adverse Drug Reactions
Current Medicinal Chemistry Anti-inflammatory Potential of GSK-3 Inhibitors
Current Drug Targets