Abstract
Halogen bonds are short-range molecular interactions that are analogous to classical hydrogen bonds, except that a polarized halogen replaces the hydrogen as the acid in the Lewis acid/base pair. Such interactions occur regularly in the structures of many ligand-protein complexes, but have only recently been recognized in biological systems as a distinct class with well-defined physical characteristics. In this review, we survey twelve single crystal structures of protein kinase complexes with halogenated ligands in order to characterize the role of halogen bonds in conferring specificity and affinity for halogenated inhibitors in this important class of enzymes. From this survey, we attempt to identify the properties of halogen bonds that can be generally applied to bottom-up strategies for designing inhibitors for this and other enzyme targets.
Keywords: Halogen bond, protein kinase, rational drug design
Current Topics in Medicinal Chemistry
Title: The Role of Halogen Bonding in Inhibitor Recognition and Binding by Protein Kinases
Volume: 7 Issue: 14
Author(s): Voth Regier Andrea and Ho Shing P.
Affiliation:
Keywords: Halogen bond, protein kinase, rational drug design
Abstract: Halogen bonds are short-range molecular interactions that are analogous to classical hydrogen bonds, except that a polarized halogen replaces the hydrogen as the acid in the Lewis acid/base pair. Such interactions occur regularly in the structures of many ligand-protein complexes, but have only recently been recognized in biological systems as a distinct class with well-defined physical characteristics. In this review, we survey twelve single crystal structures of protein kinase complexes with halogenated ligands in order to characterize the role of halogen bonds in conferring specificity and affinity for halogenated inhibitors in this important class of enzymes. From this survey, we attempt to identify the properties of halogen bonds that can be generally applied to bottom-up strategies for designing inhibitors for this and other enzyme targets.
Export Options
About this article
Cite this article as:
Andrea Regier Voth and P. Shing Ho, The Role of Halogen Bonding in Inhibitor Recognition and Binding by Protein Kinases, Current Topics in Medicinal Chemistry 2007; 7 (14) . https://dx.doi.org/10.2174/156802607781696846
DOI https://dx.doi.org/10.2174/156802607781696846 |
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
-
Patent Annotations
Recent Patents on CNS Drug Discovery (Discontinued) Current Quest in Natural Bioactive Compounds for Alzheimer’s Disease: Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based Evidence
Current Drug Targets Mast Cell – Glia Dialogue in Chronic Pain and Neuropathic Pain: Blood-Brain Barrier Implications
CNS & Neurological Disorders - Drug Targets Neuroprotection: The Emerging Concept of Restorative Neural Stem Cell Biology for the Treatment of Neurodegenerative Diseases
Current Neuropharmacology Other Proteins Involved in Parkinson's Disease and Related Disorders
Current Protein & Peptide Science Patent Selections
Recent Patents on DNA & Gene Sequences Exploring Nitrostyrene as a Scaffold for a New Class a of Monoamine Oxidase Inhibitors
Letters in Drug Design & Discovery FTIR Spectroscopy Analysis can Highlight Induced Damage in Neuronallike Cells and Bio-protective Effectiveness of Agmatine
Current Metabolomics EDITORIAL (Natural Products for Treatment of Alzheimer's Disease and Related Diseases: Understanding their Mechanism of Action)
Current Neuropharmacology Editorial [Hot Topic: The Medicinal Chemistry of Hybrid-Based Drugs Targeting Multiple Sites of Action (Guest Editors: Jose Marco-Contelles, & Elena Soriano)]
Current Topics in Medicinal Chemistry cGAS-STING-mediated IFN-I Response in Host Defense and Neuroinflammatory Diseases
Current Neuropharmacology Neuroprotective Role of Agmatine in Neurological Diseases
Current Neuropharmacology Hematopoietic Stem Cells Therapies
Current Stem Cell Research & Therapy Multifunctional Ligands Targeting Phosphodiesterase as the Future Strategy for the Symptomatic and Disease-Modifying Treatment of Alzheimer’s Disease
Current Medicinal Chemistry Neuronal Death in Amyotrophic Lateral Sclerosis (ALS): What Can We Learn from Genetics?
CNS & Neurological Disorders - Drug Targets Isoprostanes as Biomarkers and Mediators of Oxidative Injury in Infant and Adult Central Nervous System Diseases
Current Neurovascular Research Significance of P2X7 Receptor Variants to Human Health and Disease
Recent Patents on DNA & Gene Sequences Cell-Replacement Therapy with Stem Cells in Neurodegenerative Diseases
Current Neurovascular Research Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease
Current Alzheimer Research Morphofunctional Aspects of the Blood-Brain Barrier
Current Drug Metabolism