Journal ArticleDOI
Stabilization and structure of telomeric and c-myc region intramolecular G-quadruplexes: the role of central cations and small planar ligands.
TLDR
The authors' results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed, and end stacking is shown to be the dominant mode for ligand attachment.Abstract:
A promising approach for anticancer strategies is the stabilization of telomeric DNA into a G-quadruplex structure. To explore the intrinsic stabilization of folded G-quadruplexes, we combined electrospray ionization mass spectrometry, ion mobility spectrometry, and molecular modeling studies to study different DNA sequences known to form quadruplexes. Two telomeric DNA sequences of different lengths and two DNA sequences derived from the NHE III1 region of the c-myc oncogene (Pu22 and Pu27) were studied. NH4+ and the ligands PIPER, TMPyP4, and the three quinacridines MMQ1, MMQ3, and BOQ1 were complexed with the DNA sequences to determine their effect on the stability of the G-quadruplexes. Our results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed. Furthermore, the ligands can be classified according to their ability to stabilize the quadruplexes and end stacking is shown to be the dominant mode for ligand attachment. In all cases our solvent-free...read more
Citations
More filters
Journal ArticleDOI
A hitchhiker's guide to G-quadruplex ligands
TL;DR: The present article aims to help researchers enter this exciting research field, and to highlight recent advances in the design of G-quadruplex ligands.
Journal ArticleDOI
The application of DNA and RNA G-quadruplexes to therapeutic medicines
TL;DR: A critical review of the important underlying characteristics of G-quadruplexes that make them functional, stable, and predictable nanoscaffolds and a critical evaluation of the application of high-resolution structural biology and its ability to provide meaningful and valid models for future applications.
Journal ArticleDOI
Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA
TL;DR: A critical review of the advances in understanding of the structures and functions of human telomeres and the current efforts on developing various chemical approaches to targeting human telomerase for the treatment of cancer.
Journal ArticleDOI
Ligands playing musical chairs with G-quadruplex DNA: a rapid and simple displacement assay for identifying selective G-quadruplex binders
David Monchaud,Clémence Allain,Hélène Bertrand,Nicolas Smargiasso,Frédéric Rosu,Valérie Gabelica,A. De Cian,A. De Cian,Jean-Louis Mergny,Jean-Louis Mergny,Marie-Paule Teulade-Fichou +10 more
TL;DR: The details of G4-FID (G-quadruplex fluorescent intercalator displacement), a simple method aiming at evaluating quadruplex-DNA binding affinity and quadruplex over duplex-DNA selectivity of putative ligands, are reported here.
Journal ArticleDOI
Small Molecules Targeting c-Myc Oncogene: Promising Anti-Cancer Therapeutics
TL;DR: The abnormal over-expression of c-Myc is frequently observed in some tumors, including carcinomas of the breast, colon, and cervix, as well as small-cell lung cancer, osteosarcomas, glioblastomas, and myeloid leukemias, therefore making it a possible target for anticancer therapy.
References
More filters
Journal ArticleDOI
Creation of human tumour cells with defined genetic elements
William C. Hahn,William C. Hahn,Christopher M. Counter,Ante S. Lundberg,Ante S. Lundberg,Roderick L. Beijersbergen,Mary W. Brooks,Robert A. Weinberg +7 more
TL;DR: It is shown that the ectopic expression of the telomerase catalytic subunit (hTERT) in combination with two oncogenes results in direct tumorigenic conversion of normal human epithelial and fibroblast cells.
Journal ArticleDOI
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription.
TL;DR: The principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization is established, establishing the principle that the purine-rich strand of the DNA in this region can form two different intramolecular G- quadruplex structures.
Journal ArticleDOI
Crystal structure of parallel quadruplexes from human telomeric DNA.
TL;DR: This crystal structure of a quadruplex formed from four consecutive human telomeric DNA repeats and grown at a K+ concentration that approximates its intracellular concentration suggests a straightforward path for telomere folding and unfolding, as well as ways in which it can recognize telomerre-associated proteins.
MonographDOI
Transport properties of ions in gases
Edward A. Mason,Earl W. McDaniel +1 more
TL;DR: In this paper, the Kinetic Theory of Mobility and Diffusion is used to measure drift velocities and Longitudinal Diffusion Coefficients, and the measure of transverse diffusion coefficients.
Journal ArticleDOI
Telomeres and human disease: ageing, cancer and beyond
TL;DR: Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease.