Abstract
Whilst fragment-based screening has found significant utility in aiding the discovery of high quality hits against a range of targets, the use of this technology in the protein-protein interaction inhibitor field is very much in its infancy. This review aims to highlight the key technologies used to identify fragment hits, such as NMR, SPR, X-ray crystallography and biochemical screening, the fragmentbased protein-protein interaction case studies reported to date and, more importantly, the potential of this methodology in unearthing high quality hit molecules in this critical area of drug discovery. In addition, we also discuss some of the key aspects of fragment library design, the composition of a high quality library and suggest ways in which future, more structurally diverse fragments which occupy different regions of chemical space to the vast majority of current fragment libraries may be selected.
Keywords: Fragment-based drug discovery, protein-protein interactions, hot spots, ligand efficiency, biophysical, techniques, inhibitors, fragment libraries, diversity, NMR.
Current Pharmaceutical Design
Title:Using Fragment-Based Technologies to Target Protein-Protein Interactions
Volume: 18 Issue: 30
Author(s): Justin F. Bower and Andrew Pannifer
Affiliation:
Keywords: Fragment-based drug discovery, protein-protein interactions, hot spots, ligand efficiency, biophysical, techniques, inhibitors, fragment libraries, diversity, NMR.
Abstract: Whilst fragment-based screening has found significant utility in aiding the discovery of high quality hits against a range of targets, the use of this technology in the protein-protein interaction inhibitor field is very much in its infancy. This review aims to highlight the key technologies used to identify fragment hits, such as NMR, SPR, X-ray crystallography and biochemical screening, the fragmentbased protein-protein interaction case studies reported to date and, more importantly, the potential of this methodology in unearthing high quality hit molecules in this critical area of drug discovery. In addition, we also discuss some of the key aspects of fragment library design, the composition of a high quality library and suggest ways in which future, more structurally diverse fragments which occupy different regions of chemical space to the vast majority of current fragment libraries may be selected.
Export Options
About this article
Cite this article as:
F. Bower Justin and Pannifer Andrew, Using Fragment-Based Technologies to Target Protein-Protein Interactions, Current Pharmaceutical Design 2012; 18 (30) . https://dx.doi.org/10.2174/138161212802651689
DOI https://dx.doi.org/10.2174/138161212802651689 |
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
-
Molecular Signals Elicited by GPCR Agonists in Hypertension, Cardiovascular Remodeling: Are MMPs and ADAMs Elusive Therapeutic Targets?
Current Hypertension Reviews Overview of Cantharidin and its Analogues
Current Medicinal Chemistry The Synthesis and Antiviral Properties of Acyclic Nucleoside Analogues with a Phosphonomethoxy Fragment in the Side Chain
Current Medicinal Chemistry Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase
Recent Patents on Anti-Cancer Drug Discovery The Therapeutic Potential of Cell-Internalizing Aptamers
Current Topics in Medicinal Chemistry The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Beneficial Effect of Peptides from Microalgae on Anticancer
Current Protein & Peptide Science Drug Metabolism and Pharmacokinetics of Nanodrugs from Chinese Medicines and Natural Products
Current Drug Metabolism Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials
Current Pharmaceutical Design NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression
Anti-Cancer Agents in Medicinal Chemistry mRNA as a Versatile Tool for Exogenous Protein Expression
Current Gene Therapy Potential Cancer Gene Therapy by Baculoviral Transduction
Current Gene Therapy High Order Texture-Based Analysis in Biomedical Images
Current Medical Imaging Histone Deacetylases: Anti-Angiogenic Targets in Cancer Therapy
Current Cancer Drug Targets Mechanisms of Action of Imidazoacridinone and Triazoloacridinone Derivatives in View of their Biological Activity
Current Pharmaceutical Analysis Adipocytes Derived from Human Bone Marrow Mesenchymal Stem Cells Exert Inhibitory Effects on Osteoblastogenesis
Current Molecular Medicine Advances in the Development of Non-Human Viral DNA-Vectors for Gene Delivery
Current Gene Therapy Telomere Maintenance Mechanisms in Cancer: Clinical Implications
Current Pharmaceutical Design Identification and Targeting of Tumor Escape Mechanisms: A New Hope for Cancer Therapy?
Current Pharmaceutical Design Drug Resistance in Renal Tumors of Childhood
Current Pharmaceutical Biotechnology