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
-
Editorial [Hot topic: Drug-Induced QT Interval Prolongation: Clinical, Safety and Regulatory Update (Guest Editor: Guillermo Di Girolamo)]
Current Drug Safety Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture
Current Pharmaceutical Design Tumour-Specific Uptake of Anti-Cancer Drugs: The Future is Here
Current Drug Metabolism Therapeutic Application of Endothelial Progenitor Cells for Treatment of Cardiovascular Diseases
Current Stem Cell Research & Therapy Recent Progress of Medicinal Chemistry Research on Peroxisome Proliferator-Activated Receptor (PPAR) Ligands for the Treatment of Metabolic Syndrome
Current Bioactive Compounds Comparison Between 3D Echocardiography and Cardiac Magnetic Resonance Imaging (CMRI) in the Measurement of Left Ventricular Volumes and Ejection Fraction
Current Medical Imaging Alcohol and the Cardiovascular System: A Double-Edged Sword
Current Pharmaceutical Design Use of Nanoparticles as Therapy for Methicillin-Resistant Staphylococcus aureus Infections
Current Drug Metabolism Current and Experimental Antibody-Based Therapeutics: Insights, Breakthroughs, Setbacks and Future Directions
Current Molecular Medicine Copeptin in Preeclampsia Development
Current Women`s Health Reviews FoxO1 Inhibitors: The Future Medicine for Metabolic Disorders?
Current Diabetes Reviews Efficacy and Safety Assessment of Hypertension Management with Coveram (Perindopril/Amlodipine Fixed Combination) in Patients with Previous Angiotensin Receptor Blocker (ARB) Treatment: Arabian Gulf STRONG Study
Current Vascular Pharmacology Actual Knowledge of Systemic Inflammation Reaction During Cardiopulmonary Bypass
Recent Patents on Cardiovascular Drug Discovery Fibrinogen: A Predictor of Vascular Disease
Current Pharmaceutical Design Biological Roles of the Eclectic Chromogranin-A-derived Peptide Catestatin
Current Medicinal Chemistry Gene Therapy in Lung Transplantation
Current Gene Therapy MicroRNA Regulation in Cardiovascular Disease
Current Drug Targets Cannabinoids and Cardiovascular Disease: The Outlook for Clinical Treatments
Current Vascular Pharmacology Promising Therapies in Sickle Cell Disease
Cardiovascular & Hematological Disorders-Drug Targets The Role of Tai Chi in Mental Health Management—Lessons Learned from Clinical Trials
Reviews on Recent Clinical Trials