Abstract
Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the small molecule ligands. Common traits shared among these successful examples are identified, and formulated into potentially useful guidance for drug discovery efforts within this target class.
Current Protein & Peptide Science
Title: Drug-Like Inhibitors of Protein-Protein Interactions: A Structural Examination of Effective Protein Mimicry
Volume: 9 Issue: 3
Author(s): D. C. Fry
Affiliation:
Abstract: Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the small molecule ligands. Common traits shared among these successful examples are identified, and formulated into potentially useful guidance for drug discovery efforts within this target class.
Export Options
About this article
Cite this article as:
Fry C. D., Drug-Like Inhibitors of Protein-Protein Interactions: A Structural Examination of Effective Protein Mimicry, Current Protein & Peptide Science 2008; 9 (3) . https://dx.doi.org/10.2174/138920308784533989
DOI https://dx.doi.org/10.2174/138920308784533989 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma
Endocrine, Metabolic & Immune Disorders - Drug Targets Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells
Recent Patents on Regenerative Medicine Editorial [ Immune-Mediated Mechanisms in Atheroclerosis:Prevention and Treatment of Clinical Manifestations Executive Editor: Emilio Jirillo ]
Current Pharmaceutical Design Exosomes and Exosomal microRNAs in Age-associated Stroke
Current Vascular Pharmacology Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage
Current Molecular Pharmacology The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia
Current Topics in Medicinal Chemistry Hypertension and Endothelial Dysfunction: Therapeutic Approach
Current Vascular Pharmacology Editorial (Thematic Issue: The Life Cycle of the Heart Failure Patient)
Current Cardiology Reviews Human Use of Leucoselect® Phytosome® with Special Reference to Inflammatory- Allergic Pathologies in Frail Elderly Patients
Current Pharmaceutical Design Protrhombotic Effects of Contraceptives
Current Pharmaceutical Design Synthesis and Antiproliferative Activity of New Polyoxo 2-Benzyl-2,3- dihydrobenzofurans and Their Related Compounds
Letters in Drug Design & Discovery Targeting Drugs to APJ Receptor: The Prospect of Treatment of Hypertension and Other Cardiovascular Diseases
Current Drug Targets Molecular Determinants of the Cardiometabolic Phenotype
Endocrine, Metabolic & Immune Disorders - Drug Targets Clinical Evaluation of Anti-Obesity Drugs
Current Drug Targets Double-Edged Sword of Novel Anti-Cancer Treatment: Proteasome Inhibition in the Growth Plate Causes Impairment of Longitudinal Bone Growth
Current Pediatric Reviews Carbon Nanotube-Based Electrochemical Biosensing Platforms: Fundamentals,Applications, and Future Possibilities
Recent Patents on Biotechnology Predicting Targeted Polypharmacology for Drug Repositioning and Multi- Target Drug Discovery
Current Medicinal Chemistry The Role of Beta-Blocker in Heart Failure in Adults with Congenital Heart Disease
Reviews on Recent Clinical Trials Current Therapeutic Approaches for Targeting Inflammation in Depression and Cardiovascular Disease
Current Drug Metabolism Coronary Pressure Measurement Based Decision Making for Percutaneous Coronary Intervention
Current Cardiology Reviews