Abstract
Transcription factors are recognized as the master regulators of gene expression. Interestingly, about 10% of the transcription factors described in mammals are up to date directly implicated in a very large number of human diseases. With the exception of ligand-inducible nuclear receptors, transcription factors have longtime been considered as “undruggable” targets for therapeutics. However, the significant breakthroughs in their protein biochemistry and interactions with DNA at the structural level, together with increasing needs for new targeted-approaches particularly in cancers, has changed this postulate and opened the way for targeting transcription factors. Along with a better knowledge of their specific DNA binding sequences by genome wide and high throughput sequencing assay, these informations make possible the potent targeting of the transcription factors by three approaches dependently of their mechanism of action. In this review, we discuss the different physicochemical interactions between the transcription factors and the DNA helix, and the protein/protein interactions within a transcription factor complex and their impacts on the DNA structure. In order to impair transcription factor activities, small molecules compounds can either act by direct interaction on the transcription factor, or by blocking the protein/protein interactions in a transcription complex, or by competing with the transcription factor itself and specifically targeting its cognate binding sequence. For this latter mode of transcription targeting, we pay special attention to the DNA intercalating, alkylating or groove binders for transcription factor/DNA binding modulation.
Keywords: Alkylating drugs, Competition, DNA binding, DNA ligands, Gene expression, Groove binders, Intercalators, Transcription factors.
Current Topics in Medicinal Chemistry
Title:Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an Approach for Controlling Gene Expression
Volume: 15 Issue: 14
Author(s): Mohamed Amine Bouhlel, Melanie Lambert and Marie-Helene David-Cordonnier
Affiliation:
Keywords: Alkylating drugs, Competition, DNA binding, DNA ligands, Gene expression, Groove binders, Intercalators, Transcription factors.
Abstract: Transcription factors are recognized as the master regulators of gene expression. Interestingly, about 10% of the transcription factors described in mammals are up to date directly implicated in a very large number of human diseases. With the exception of ligand-inducible nuclear receptors, transcription factors have longtime been considered as “undruggable” targets for therapeutics. However, the significant breakthroughs in their protein biochemistry and interactions with DNA at the structural level, together with increasing needs for new targeted-approaches particularly in cancers, has changed this postulate and opened the way for targeting transcription factors. Along with a better knowledge of their specific DNA binding sequences by genome wide and high throughput sequencing assay, these informations make possible the potent targeting of the transcription factors by three approaches dependently of their mechanism of action. In this review, we discuss the different physicochemical interactions between the transcription factors and the DNA helix, and the protein/protein interactions within a transcription factor complex and their impacts on the DNA structure. In order to impair transcription factor activities, small molecules compounds can either act by direct interaction on the transcription factor, or by blocking the protein/protein interactions in a transcription complex, or by competing with the transcription factor itself and specifically targeting its cognate binding sequence. For this latter mode of transcription targeting, we pay special attention to the DNA intercalating, alkylating or groove binders for transcription factor/DNA binding modulation.
Export Options
About this article
Cite this article as:
Bouhlel Amine Mohamed, Lambert Melanie and David-Cordonnier Marie-Helene, Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an Approach for Controlling Gene Expression, Current Topics in Medicinal Chemistry 2015; 15 (14) . https://dx.doi.org/10.2174/1568026615666150413154713
DOI https://dx.doi.org/10.2174/1568026615666150413154713 |
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
-
Assessment In Vitro of a Novel Therapeutic Strategy for Glioma, Combining Herpes Simplex Virus HSV1716-mediated Oncolysis with Gene Transfer and Targeted Radiotherapy
Medicinal Chemistry PPARγ and Its Ligands: Potential Antitumor Agents in the Digestive System
Current Stem Cell Research & Therapy Thalidomide: A Banned Drug Resurged into Future Anticancer Drug
Current Drug Therapy Emerging Roles of microRNAs in the Molecular Responses to Hypoxia
Current Pharmaceutical Design Preparation and <I>In Vitro/Vivo</I> Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery
Current Drug Delivery Synthesis of [DTPA-bis(D-ser)] Chelate (DBDSC): An Approach for the Design of SPECT Radiopharmaceuticals Based on Technetium
Current Radiopharmaceuticals Sphere Formation Assay is not an Effective Method for Cancer Stem Cell Derivation and Characterization from the Caco-2 Colorectal Cell Line
Current Stem Cell Research & Therapy The Membrane-targeted Alkylphosphocholine Erufosine Interferes with Survival Signals from the Extracellular Matrix
Anti-Cancer Agents in Medicinal Chemistry Taxotere Chemosensitivity Evaluation in Rat Breast Tumor by Multimodal Imaging: Quantitative Measurement by Fusion of MRI, PET Imaging with MALDI and Histology
Recent Patents on Medical Imaging Nanomedicines Based Drug Delivery Systems for Anti-Cancer Targeting and Treatment
Current Drug Delivery MicroRNA Functions and Potential Clinical Utility in Glioblastoma
Current Signal Transduction Therapy Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Current Topics in Medicinal Chemistry The Current State of Potential Therapeutic Modalities for Glioblastoma Multiforme: A Clinical Review
Current Drug Metabolism Flavonoids: The Innocuous Agents Offering Protection against Alzheimer’s Disease Through Modulation of Proinflammatory and Apoptotic Pathways
Current Topics in Medicinal Chemistry Post-Wortmannin Era: Novel Phosphoinositide 3-Kinase Inhibitors with Potential Therapeutic Applications
Current Enzyme Inhibition Thalidomide Analogues as Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery CEST MRI for Molecular Imaging of Brain Metabolites
Current Molecular Imaging (Discontinued) Peptide-Receptor Ligands and Multivalent Approach
Anti-Cancer Agents in Medicinal Chemistry Adding to the Mix: Fibroblast Growth Factor and Platelet-Derived Growth Factor Receptor Pathways as Targets in Non – small Cell Lung Cancer
Current Cancer Drug Targets Antiangiogenic Drugs and Tyrosine Kinases
Anti-Cancer Agents in Medicinal Chemistry