Abstract
Integrins are a family of heterodimeric receptors, which modulate many cellular processes including: growth, death (apoptosis), adhesion, migration, and invasion by activating several signaling pathways. Integrin-binding RGD (arginine- glycine-aspartic acid) is found in several important extracellular matrix proteins which serve as adhesive integrin ligands. The RGD motif has also been found in many toxins from snake venom and other sources that specifically inhibit integrin binding function and serve as potent integrin antagonists, particularly of platelet aggregation and integrinmediated cell adhesion. Many of these proteins have potential as therapeutic agents which can target integrins directly. Structural and functional studies of several RGD-containing toxins suggest that the inhibitory potency of these proteins lies in subtle positional requirements of the tripeptide RGD at the tip of a flexible loop, a structural feature for binding to integrins. In addition, amino acid residues in this loop in close vicinity to the RGD-motif determine the integrin-binding specificity and selectivity. This review will present a review of integrin structure and function, and of disintegrin structural features responsible for their activity as antagonists of integrin function. The use of integrins in drug targeting and integrins as targets for drug delivery by using the RGD as a template structure will also be discussed
Keywords: ADAM proteins, antagonist, cell adhesion, disintegrin, integrin, platelet aggregation, RGD-motif, venom toxins
Current Pharmaceutical Design
Title: Integrins in Drug Targeting-RGD Templates in Toxins
Volume: 12 Issue: 22
Author(s): X. Lu, D. Lu, M. F. Scully and V. V. Kakkar
Affiliation:
Keywords: ADAM proteins, antagonist, cell adhesion, disintegrin, integrin, platelet aggregation, RGD-motif, venom toxins
Abstract: Integrins are a family of heterodimeric receptors, which modulate many cellular processes including: growth, death (apoptosis), adhesion, migration, and invasion by activating several signaling pathways. Integrin-binding RGD (arginine- glycine-aspartic acid) is found in several important extracellular matrix proteins which serve as adhesive integrin ligands. The RGD motif has also been found in many toxins from snake venom and other sources that specifically inhibit integrin binding function and serve as potent integrin antagonists, particularly of platelet aggregation and integrinmediated cell adhesion. Many of these proteins have potential as therapeutic agents which can target integrins directly. Structural and functional studies of several RGD-containing toxins suggest that the inhibitory potency of these proteins lies in subtle positional requirements of the tripeptide RGD at the tip of a flexible loop, a structural feature for binding to integrins. In addition, amino acid residues in this loop in close vicinity to the RGD-motif determine the integrin-binding specificity and selectivity. This review will present a review of integrin structure and function, and of disintegrin structural features responsible for their activity as antagonists of integrin function. The use of integrins in drug targeting and integrins as targets for drug delivery by using the RGD as a template structure will also be discussed
Export Options
About this article
Cite this article as:
Lu X., Lu D., Scully F. M. and Kakkar V. V., Integrins in Drug Targeting-RGD Templates in Toxins, Current Pharmaceutical Design 2006; 12 (22) . https://dx.doi.org/10.2174/138161206777947713
DOI https://dx.doi.org/10.2174/138161206777947713 |
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
-
Seeking the 5th Base of DNA Using Chromatographic Methods of Analysis
Current Organic Chemistry Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design Quantitative Structure-Activity Relationship Studies: Understanding the Mechanism of Tyrosine Kinase Inhibition
Current Enzyme Inhibition Activation of PI3K/Akt/mTOR Pathway and Dual Inhibitors of PI3K and mTOR in Endometrial Cancer
Current Medicinal Chemistry Biology of Cox-2: An Application in Cancer Therapeutics
Current Drug Targets Integrin α4β7 Antagonists: Activities, Mechanisms of Action and Therapeutic Prospects
Current Immunology Reviews (Discontinued) The Use of Nimesulide and Its Analogues in Cancer Chemoprevention
Anti-Cancer Agents in Medicinal Chemistry Issues Impacting Therapeutic Outcomes in Pediatric Patients: An Overview
Current Pediatric Reviews Fluorescent Molecular Imaging: Technical Progress and Current Preclinical and Clinical Applications in Urogynecologic Diseases
Current Molecular Medicine Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry Aquaporin Biology and Nervous System
Current Neuropharmacology The Impact of Tumor Physiology on Camptothecin-Based Drug Development
Current Medicinal Chemistry - Anti-Cancer Agents Molecular and Genetic Profiling of Prostate Cancer: Implications for Future Therapy
Current Cancer Therapy Reviews NF-κB, a Potential Therapeutic Target for the Treatment of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Functions of S100 Proteins
Current Molecular Medicine The Relevance of Supplemental Vitamin D in Malignancies
Anti-Cancer Agents in Medicinal Chemistry TRPM8: From Cold to Cancer, Peppermint to Pain
Current Pharmaceutical Biotechnology Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues
Drug Metabolism Letters Radiotracers in Oncology
Current Radiopharmaceuticals Nongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry