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.
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 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Endothelial Dysfunction and the Effects of TNF Inhibitors on the Endothelium in Psoriasis and Psoriatic Arthritis: A Systematic Review
Current Pharmaceutical Design Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy
Current Hypertension Reviews Hematopoietic Progenitor and Stem Cells Circulate by Surfing on Intracellular Ca2+ Waves: A Novel Target for Cell-based Therapy and Anti-cancer Treatment?
Current Signal Transduction Therapy Tackling Cardiovascular Risk: New Evidence from Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Vitamins in the Prevention or Delay of Cognitive Disability of Aging
Current Aging Science Pharmaceuticals and Cosmeceuticals Based on Soft Nanotechnology Techniques with Antioxidative, Immunostimulative and other Therapeutic Activities
Recent Patents on Nanotechnology Potential Impact of Genetic Variants in Nrf2 Regulated Antioxidant Genes and Risk Prediction of Diabetes and Associated Cardiac Complications
Current Medicinal Chemistry The Role of Antithrombotic Therapy in Heart Failure
Current Pharmaceutical Design Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry A Review on Novel Ligand Targeted Delivery for Cardiovascular Disorder
Current Drug Delivery The Mediterranean and other Dietary Patterns in Secondary Cardiovascular Disease Prevention: A Review
Current Vascular Pharmacology Inverse Regulation of MMP-9 and MMP-2 in Long-Term Follow-up After Acute Coronary Syndrome: Lack of Correlation with Platelet and Endothelial Cell Activation Markers
Vascular Disease Prevention (Discontinued) Autophagy in Diabetic Retinopathy
Current Neuropharmacology Meet Our Editorial Board Member
Current Drug Targets The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age
Current Neuropharmacology Hyperpolarized Metabolic MR in the Study of Cardiac Function and Disease
Current Pharmaceutical Design Mesenchymal Stromal Cell Therapy for Cardio Renal Disorders
Current Pharmaceutical Design The Vernakalant Story: How Did It Come to Approval in Europe and What is the Delay in the U.S.A?
Current Cardiology Reviews Ivabradine for Treatment of Coronary Artery Disease: From Last Chance Resort to Mainstem of a Reasoned Therapy
Cardiovascular & Hematological Agents in Medicinal Chemistry Pharmacological Risk Factors for Delirium after Cardiac Surgery: A Review
Current Neuropharmacology