Abstract
In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.
Keywords: Drug discovery, FBDD, FBLD, Fragment-based drug design, HTS by NMR, PPIs, Protein-protein interactions, Positional scanning.
Current Topics in Medicinal Chemistry
Title:High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists
Volume: 15 Issue: 20
Author(s): Bainan Wu, Elisa Barile, Surya K. De, Jun Wei, Angela Purves and Maurizio Pellecchia
Affiliation:
Keywords: Drug discovery, FBDD, FBLD, Fragment-based drug design, HTS by NMR, PPIs, Protein-protein interactions, Positional scanning.
Abstract: In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.
Export Options
About this article
Cite this article as:
Wu Bainan, Barile Elisa, De K. Surya, Wei Jun, Purves Angela and Pellecchia Maurizio, High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists, Current Topics in Medicinal Chemistry 2015; 15 (20) . https://dx.doi.org/10.2174/1568026615666150519102459
DOI https://dx.doi.org/10.2174/1568026615666150519102459 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Laboratory Techniques for Human Viral Encephalitis Diagnosis
Infectious Disorders - Drug Targets Artemisia Species as a New Candidate for Diabetes Therapy: A Comprehensive Review
Current Molecular Medicine Irreversible Protein Kinase Inhibitors
Current Medicinal Chemistry Review of the Contribution of Radiolabelled Tracers for Tumour Cell Status Imaging
Current Medical Imaging Obesity and Cancer: Biological Links and Treatment Implications
Current Cancer Drug Targets Stem Cells and Bioactive Scaffolds as a Treatment for Traumatic Brain Injury
Current Stem Cell Research & Therapy Development of Novel Cardiovascular Therapeutics From Small Regulatory RNA Molecules - An Outline of Key Requirements
Current Pharmaceutical Design Raf Inhibitors as Therapeutic Agents Against Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Arsenic Immunotoxicity and Immunomodulation by Phytochemicals: Potential Relations to Develop Chemopreventive Approaches
Recent Patents on Inflammation & Allergy Drug Discovery Biosafety Challenges for Use of Lentiviral Vectors in Gene Therapy
Current Gene Therapy Regulation of MET Receptor Signaling by SOCS1 and its Implications for Hepatocellular Carcinoma
Current Pharmaceutical Design Obesity Modulation - The Role in Carcinogenesis
Anti-Cancer Agents in Medicinal Chemistry Radiolabeled Glucose Derivatives for Tumor Imaging Using SPECT and PET
Current Medicinal Chemistry Biologics: An Update and Challenge of Their Pharmacokinetics
Current Drug Metabolism Recent Development in Nano-Sized Dosage Forms of Plant Alkaloid Camptothecin-Derived Drugs
Recent Patents on Anti-Cancer Drug Discovery Targeting Epithelial-Mesenchymal Transition Phenotype for Gastro-Intestinal Cancer
Current Pharmaceutical Design The Applicability of mTOR Inhibition in Solid Tumors
Current Cancer Drug Targets Clinical Pharmacotherapy and Drug Development for Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Drug Delivery for Cancer Immunotherapy and Vaccines
Pharmaceutical Nanotechnology Animal Venoms have Potential to Treat Cancer
Current Topics in Medicinal Chemistry