Abstract
Expansion of trinucleotide repeats (TNRs) within genes plays a major role in pathology of various neurological diseases. The correlations of these unusual repetitive sequences with the aetiology of these diseases and the mechanism by which those repeats are expanded during replication have been extensively studied. Small-molecule ligands that bind to TNRs could provide potent biological applications. First, the length of the TNR is the most important determinant of these neurological diseases. Ligands that reduce the repeat length or impair repeat expansion may be used to delay onset and reduce the severity of these diseases. Interestingly, many important anticancer ligands and antibiotics have desirable qualities when interacting with TNR DNA, and may form the basis for the development of novel therapeutics against neurological diseases. Second, designed ligands that bind to expanded TNRs with high specificity based on the structural and chemical characteristics of these repeats can serve as diagnostic tools for determining repeat length and may have applications in preventive medicine. In this article we will review our current understanding of the interaction between DNA-binding ligands and TNRs.
Keywords: Diagnosis, DNA expansion, Neurological disease, Therapy, TNRs-acting ligands, Trinucleotide repeats.
Current Topics in Medicinal Chemistry
Title:The Interaction of DNA-Binding Ligands with Trinucleotide-Repeat DNA: Implications for Therapy and Diagnosis of Neurological Disorders
Volume: 15 Issue: 14
Author(s): Chung-ke Chang, Cyong-Ru Jhan and Ming-Hon Hou
Affiliation:
Keywords: Diagnosis, DNA expansion, Neurological disease, Therapy, TNRs-acting ligands, Trinucleotide repeats.
Abstract: Expansion of trinucleotide repeats (TNRs) within genes plays a major role in pathology of various neurological diseases. The correlations of these unusual repetitive sequences with the aetiology of these diseases and the mechanism by which those repeats are expanded during replication have been extensively studied. Small-molecule ligands that bind to TNRs could provide potent biological applications. First, the length of the TNR is the most important determinant of these neurological diseases. Ligands that reduce the repeat length or impair repeat expansion may be used to delay onset and reduce the severity of these diseases. Interestingly, many important anticancer ligands and antibiotics have desirable qualities when interacting with TNR DNA, and may form the basis for the development of novel therapeutics against neurological diseases. Second, designed ligands that bind to expanded TNRs with high specificity based on the structural and chemical characteristics of these repeats can serve as diagnostic tools for determining repeat length and may have applications in preventive medicine. In this article we will review our current understanding of the interaction between DNA-binding ligands and TNRs.
Export Options
About this article
Cite this article as:
Chang Chung-ke, Jhan Cyong-Ru and Hou Ming-Hon, The Interaction of DNA-Binding Ligands with Trinucleotide-Repeat DNA: Implications for Therapy and Diagnosis of Neurological Disorders, Current Topics in Medicinal Chemistry 2015; 15 (14) . https://dx.doi.org/10.2174/1568026615666150413155030
DOI https://dx.doi.org/10.2174/1568026615666150413155030 |
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
-
Crosstalk between Inflammation and the BBB in Stroke
Current Neuropharmacology Role of Cytokines in Neurological Disorders
Current Medicinal Chemistry Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders
Current Medicinal Chemistry Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants
Current Neuropharmacology Colloidal Polymeric Nanoparticles and Brain Drug Delivery
Current Drug Delivery University of Kentucky Sanders-Brown Healthy Brain Aging Volunteers: Donor Characteristics, Procedures and Neuropathology
Current Alzheimer Research Therapeutic Benefits of <i>Piper nigrum</i>: A Review
Current Bioactive Compounds Use of Intravenous Immunoglobulin in the Treatment of Immune-Mediated Demyelinating Diseases of the Nervous System
Current Pharmaceutical Design An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Advances in Neuroimaging for HIV-1 Associated Neurological Dysfunction: Clues to the Diagnosis, Pathogenesis and Therapeutic Monitoring
Current HIV Research Gastrointestinal Immune System and Brain Dialogue Implicated in Neuroinflammatory and Neurodegenerative Diseases
Current Molecular Medicine Synthesis and Biological Evaluation of New 4-Thiazolidinone Derivatives as Carbonic Anhydrase Inhibitors
Letters in Organic Chemistry Physiology and Pathophysiology of Na+/H+ Exchange Isoform 1 in the Central Nervous System
Current Neurovascular Research The Therapeutic Role of Lamotrigine and Topiramate in A Depressive Patient with Anxiety Symptoms and Cognitive Decline: Neurometabolic Correlates
Current Clinical Pharmacology Relationship Between Susceptibility to DMCM-Induced Generalized Motor Convulsions and Low-Affinity [3H]-Ouabain Binding in Membranes in Rat Brain
Current Molecular Pharmacology The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment
CNS & Neurological Disorders - Drug Targets Graphical Abstracts:
Central Nervous System Agents in Medicinal Chemistry Carvacrol as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic Review Article
CNS & Neurological Disorders - Drug Targets Identifying Endogenous Neural Stem Cells in the Adult Brain In Vitro and In Vivo: Novel Approaches
Current Pharmaceutical Design Aldehyde Dehydrogenase as a Marker for Stem Cells
Current Stem Cell Research & Therapy