Abstract
Rho GTPases represent a family of small GTP-binding proteins that are involved in many important cellular functions relevant to cancer including cell cytoskeleton organization, migration, transcription, and proliferation. Since deregulation of members of Rho GTPase family is often found associated with many disease states, targeting of Rho GTPases and related signaling pathways for potential therapeutic benefits has been extensively pursued. Recent progress in this field of studies by peptide and peptidomemic inhibitors has provided important validations to this principle. The possibility to design and synthesize specific peptides that can bind to specific surface of the targeting proteins to elicit transient and specific blockade of the signal flows that require defined protein-protein interactions makes peptide inhibitors an attractive approach. In this review we summarize the recent advances in the design and application of a number of polypeptide and peptidomimetic structures that specifically target individual members of Rho GTPases and their up- or down-stream signaling regulators/effectors with an emphasis on cancer, inflammation and neurodegenerative diseases. The principle derived from the peptidic inhibitors has led to discoveries of the first generation of small molecule inhibitors of Rac GTPase of the Rho family. The implication of these studies in the pathobiology of various human diseases makes targeting Rho GTPases a valid strategy for future therapies.
Keywords: Rho GTPases, signaling, targeting, peptide inhibitors, therapeutics, cancer
Current Pharmaceutical Design
Title: Targeting Rho GTPases by Peptidic Structures
Volume: 15 Issue: 21
Author(s): Filippo Marchioni and Yi Zheng
Affiliation:
Keywords: Rho GTPases, signaling, targeting, peptide inhibitors, therapeutics, cancer
Abstract: Rho GTPases represent a family of small GTP-binding proteins that are involved in many important cellular functions relevant to cancer including cell cytoskeleton organization, migration, transcription, and proliferation. Since deregulation of members of Rho GTPase family is often found associated with many disease states, targeting of Rho GTPases and related signaling pathways for potential therapeutic benefits has been extensively pursued. Recent progress in this field of studies by peptide and peptidomemic inhibitors has provided important validations to this principle. The possibility to design and synthesize specific peptides that can bind to specific surface of the targeting proteins to elicit transient and specific blockade of the signal flows that require defined protein-protein interactions makes peptide inhibitors an attractive approach. In this review we summarize the recent advances in the design and application of a number of polypeptide and peptidomimetic structures that specifically target individual members of Rho GTPases and their up- or down-stream signaling regulators/effectors with an emphasis on cancer, inflammation and neurodegenerative diseases. The principle derived from the peptidic inhibitors has led to discoveries of the first generation of small molecule inhibitors of Rac GTPase of the Rho family. The implication of these studies in the pathobiology of various human diseases makes targeting Rho GTPases a valid strategy for future therapies.
Export Options
About this article
Cite this article as:
Marchioni Filippo and Zheng Yi, Targeting Rho GTPases by Peptidic Structures, Current Pharmaceutical Design 2009; 15 (21) . https://dx.doi.org/10.2174/138161209788682334
DOI https://dx.doi.org/10.2174/138161209788682334 |
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
-
Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses
Recent Patents on Anti-Cancer Drug Discovery Exercise-Induced Cardiac Troponin Release: Real-Life Clinical Confusion
Current Medicinal Chemistry Nonviral Gene Therapy and its Delivery Systems
Current Pharmaceutical Biotechnology Heme Oxygenase in Regulation of Renal Function and Blood Pressure
Current Hypertension Reviews Antioxidant Properties of Crocus Sativus L. and Its Constituents and Relevance to Neurodegenerative Diseases; Focus on Alzheimer’s and Parkinson’s Disease
Current Neuropharmacology Suppression of NF-κB Signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer
Current Cancer Drug Targets Actions of Adjunctive Nutritional Antioxidants in Periodontitis and Prevalent Systemic Inflammatory Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Is there a Relationship between Endothelial Dysfunction of the Brachial Artery, Carotid Intima-Media Thickness and Soluble Receptors of Tumor Necrosis Factor-Alpha?
Vascular Disease Prevention (Discontinued) Recent Advances in Sepsis Research: Novel Biomarkers and Therapeutic Targets
Current Medicinal Chemistry SUMOylation in Neurological Diseases
Current Molecular Medicine Angiotensin II Blockade and Renal Protection
Current Pharmaceutical Design Diabetes and Its Complications: Therapies Available, Anticipated and Aspired
Current Diabetes Reviews Renal Protective Effect of Metabolic Therapy in Patients with Coronary Artery Disease and Diabetes: From Bench to Bed Side
Current Pharmaceutical Design Therapy Against Reperfusion-induced Microvascular Injury
Current Pharmaceutical Design Recent Patents in Cardiac Resynchronization Therapy
Recent Patents on Biomedical Engineering (Discontinued) Application of Cardiac Molecular Imaging Using Positron Emission Tomography in Evaluation of Drug and Therapeutics for Cardiovascular Disorders
Current Pharmaceutical Design Radial Distribution of Elasticity in Porcine Thoracic Aorta
Vascular Disease Prevention (Discontinued) Lifestyle Factors and Endothelial Function
Current Vascular Pharmacology Calcium Store Stability as an Antiarrhythmic Endpoint
Current Pharmaceutical Design Synthesis, Molecular Targets, and Antitumor Activities of Substituted Tetrahydro-1- Oxopyrano[4,3-b][1]Benzopyrans and Nanogels for Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry