Abstract
In efforts to find agents with improved biological activity against cancer cells, recent years have seen an increased interest in the study of small molecules able to bind the deoxyribonucleic acid (DNA) when it assumes secondary structures known as G-quadruplexes (G4s) preferring them over the B form. Currently, several compounds reported in literature have already shown to be good candidates as G4s DNA stabilizers. Even though some specific features for the G4s affinity are known, such as a π-delocalized system able to stack at the top/end of a G-tetrad and positively charged substituents able to interact with the grooves, it is not clear yet what kind of structural features affect more the G4 arrangement. This is mainly due to the structure heterogeneity of both the G4 stabilizer compounds and the DNA G4s isoforms. In this review, we aim to classify some known G4 binders by analyzing them from a new perspective surprisingly never approached up to date: the symmetry features. Molecular symmetry could be responsible for the specific binding mode to the G4- DNA but could also be crucial in determining different isoform affinity. We propose to classify the G4s stabilizers in five main point group symmetry classes. This classification could be useful to design new ligands able to stabilize a specific G-quadruplex isoform, in order to increase the selectivity of new potential anticancer G-quadruplex targeting drugs, a goal yet highly sought by researchers.
Keywords: Anticancer drugs, DNA G-quadruplex, host-guest complexes, ligand symmetry, point group symmetry.
Current Medicinal Chemistry
Title:Does Ligand Symmetry Play a Role in the Stabilization of DNA G-Quadruplex Host-Guest Complexes?
Volume: 21 Issue: 23
Author(s): Antonino Lauria, Alessio Terenzi, Roberta Bartolotta, Riccardo Bonsignore, Ugo Perricone, Marco Tutone, Annamaria Martorana, Giampaolo Barone and Anna Maria Almerico
Affiliation:
Keywords: Anticancer drugs, DNA G-quadruplex, host-guest complexes, ligand symmetry, point group symmetry.
Abstract: In efforts to find agents with improved biological activity against cancer cells, recent years have seen an increased interest in the study of small molecules able to bind the deoxyribonucleic acid (DNA) when it assumes secondary structures known as G-quadruplexes (G4s) preferring them over the B form. Currently, several compounds reported in literature have already shown to be good candidates as G4s DNA stabilizers. Even though some specific features for the G4s affinity are known, such as a π-delocalized system able to stack at the top/end of a G-tetrad and positively charged substituents able to interact with the grooves, it is not clear yet what kind of structural features affect more the G4 arrangement. This is mainly due to the structure heterogeneity of both the G4 stabilizer compounds and the DNA G4s isoforms. In this review, we aim to classify some known G4 binders by analyzing them from a new perspective surprisingly never approached up to date: the symmetry features. Molecular symmetry could be responsible for the specific binding mode to the G4- DNA but could also be crucial in determining different isoform affinity. We propose to classify the G4s stabilizers in five main point group symmetry classes. This classification could be useful to design new ligands able to stabilize a specific G-quadruplex isoform, in order to increase the selectivity of new potential anticancer G-quadruplex targeting drugs, a goal yet highly sought by researchers.
Export Options
About this article
Cite this article as:
Lauria Antonino, Terenzi Alessio, Bartolotta Roberta, Bonsignore Riccardo, Perricone Ugo, Tutone Marco, Martorana Annamaria, Barone Giampaolo and Almerico Maria Anna, Does Ligand Symmetry Play a Role in the Stabilization of DNA G-Quadruplex Host-Guest Complexes?, Current Medicinal Chemistry 2014; 21 (23) . https://dx.doi.org/10.2174/0929867321666140217155156
DOI https://dx.doi.org/10.2174/0929867321666140217155156 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Gene Therapy Based on Lipid Nanoparticles as Non-viral Vectors for Glioma Treatment
Current Gene Therapy CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Heme Oxygenase -1 Gene Therapy: Recent Advances and Therapeutic Applications
Current Gene Therapy Palladacycles as Antimicrobial Agents
Current Medicinal Chemistry A Nanoparticle-Encapsulated Non-Nucleoside Reverse-Transcriptase Inhibitor with Enhanced Anti-HIV-1 Activity and Prolonged Circulation Time in Plasma
Current Pharmaceutical Design Reactions of Hydrazones with Lead Tetraacetate in Organic Synthesis
Current Organic Chemistry Delivering RNA Interference to the Mammalian Brain
Current Gene Therapy A Role for Calcineurin in Alzheimers Disease
Current Neuropharmacology Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review
Current Genomics RAGE: A Potential Target for Aβ-Mediated Cellular Perturbation in Alzheimers Disease
Current Molecular Medicine Tumor Dormancy and the Angiogenic Switch: Possible Implications of Bone Marrow- Derived Cells
Current Pharmaceutical Design Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications
Current Drug Metabolism Subject Index to Volume 3
Current Gene Therapy <sup>90</sup>Y-DOTA-Nimotuzumab: Synthesis of a Promising β− Radiopharmaceutical
Current Radiopharmaceuticals ErbB Antagonists Patenting: “Playing Chess with Cancer”
Recent Patents on Biotechnology microRNA as Biomarkers and Regulator of Cardiovascular Development and Disease
Current Pharmaceutical Design OX40 and OX40L Interaction in Cancer
Current Medicinal Chemistry The Chemical Defensive System in the Pathobiology of Idiopathic Environment- Associated Diseases
Current Drug Metabolism Transposons for Gene Therapy!
Current Gene Therapy Radiochemical Evaluation and <i>In Vitro</i> Assessment of the Targeting Ability of a Novel <sup>99m</sup>Tc-HYNIC-RGD for U87MG Human Brain Cancer Cells
Current Radiopharmaceuticals