Abstract
DNA interactive agents have been used in the clinical setting for the treatment of cancer since the beginning of modern-era chemotherapy. Despite a shift of focus towards molecular targeted therapy, DNA remains a critical macromolecular target for anti-cancer intervention and the next generation of agents must conform to the optimum combination of increased therapeutic activity and reduced off-target toxicity. We evaluate the potential of non-covalent DNA binding small molecules as “gene-control” agents, exploiting inherent or engineered sequence selectivity, to target critical genomic sequences. In addition we review examples of natural products and synthetic derivatives that exert their activity through sequence specific DNA-covalent modification.
Keywords: Alkylating agents, Anticancer chemotherapeutics, Covalent binding, DNA recognition, DNA-targeting agents, Non-covalent binding, Polyamides, Sequence specificity.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:Therapeutic Agents Based on DNA Sequence Specific Binding
Volume: 15 Issue: 14
Author(s): Luke Pett, John A. Hartley and Konstantinos Kiakos
Affiliation:
Keywords: Alkylating agents, Anticancer chemotherapeutics, Covalent binding, DNA recognition, DNA-targeting agents, Non-covalent binding, Polyamides, Sequence specificity.
Abstract: DNA interactive agents have been used in the clinical setting for the treatment of cancer since the beginning of modern-era chemotherapy. Despite a shift of focus towards molecular targeted therapy, DNA remains a critical macromolecular target for anti-cancer intervention and the next generation of agents must conform to the optimum combination of increased therapeutic activity and reduced off-target toxicity. We evaluate the potential of non-covalent DNA binding small molecules as “gene-control” agents, exploiting inherent or engineered sequence selectivity, to target critical genomic sequences. In addition we review examples of natural products and synthetic derivatives that exert their activity through sequence specific DNA-covalent modification.
Export Options
About this article
Cite this article as:
Pett Luke, A. Hartley John and Kiakos Konstantinos, Therapeutic Agents Based on DNA Sequence Specific Binding, Current Topics in Medicinal Chemistry 2015; 15 (14) . https://dx.doi.org/10.2174/1568026615666150413155431
DOI https://dx.doi.org/10.2174/1568026615666150413155431 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Cognitive Function and Heart Failure: The Role of the Adrenergic System
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Inflammation in Coronary Artery Disease and Acute Myocardial Infarction - is the Stage Set for Novel Therapies?
Current Pharmaceutical Design Current Treatment Strategies for Non-Alcoholic Fatty Liver Disease (NAFLD)
Current Drug Discovery Technologies Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?
Current Vascular Pharmacology Nano Traditional Chinese Medicine: Current Progresses and Future Challenges
Current Drug Targets Ghrelin as a Potential Anti-Obesity Target
Current Pharmaceutical Design The Prevention of Adverse Drug Reactions in Older Subjects
Current Drug Metabolism Old And New Oral Anticoagulants In Management Of Atrial Fibrillation: A Double-Edged Sword For Women
Current Vascular Pharmacology Clinical Pharmacology of Cyclophosphamide and Ifosfamide
Current Drug Therapy Antioxidant Capacity, Phytochemical Analysis and Identification of Active Compounds in Anchomanes difformis
The Natural Products Journal The Gender Bender effect in Periodontal Immune Response
Endocrine, Metabolic & Immune Disorders - Drug Targets A Giant Internal Iliac Artery Aneurysm with Arteriovenous Fistulization
Current Medical Imaging Statins as Anti-Inflammatory Agents in Atherogenesis: Molecular Mechanisms and Lessons from the Recent Clinical Trials
Current Pharmaceutical Design Use of Angiotensin Receptor Blockers and Risk of Alzheimer’s Disease: A Class Effect?
Current Reviews in Clinical and Experimental Pharmacology Carotenoids of Microalgae Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Drugs, Trials and Pathogenesis: Will Connecting these Help us Understand SLE?
Current Rheumatology Reviews Microenvironmental Interactions in Chronic Lymphocytic Leukemia: Hints for Pathogenesis and Identification of Targets for Rational Therapy
Current Pharmaceutical Design Advances in Matrix Metalloproteinase Inhibitors Based on Pyrrolidine Scaffold
Current Medicinal Chemistry Inflammatory Arthritis and Heart Disease
Current Pharmaceutical Design Long-term Etanercept Therapy Favors Weight Gain and Ameliorates Cachexia in Rheumatoid Arthritis Patients: Roles of Gut Hormones and Leptin
Current Pharmaceutical Design