Variation of DNA conformation is important in regulating gene expression and mediating drug-DNA interactions. However, directly probing transient DNA conformation changes is challenging owing to the dynamic nature of this process. We show a label-free fluorescence method to monitor transient DNA conformation changes in DNA structures with various lengths and shapes using a DNA intercalator, K21. K21 can form transient excimers on the surface of DNA; the ratiometric emission of monomer and excimer correlate to DNA transient conformation stability in numerous DNA structures, including i-motifs, G-quadruplex structures, and single nucleotide mutation at random position. We analyzed the conformation dynamics of a single plasmid before and after enzyme digestion with confocal fluorescence microscopy. This method provides a label-free fluorescence strategy to probe transient conformation changes of DNA structures and has potential in uncovering transient genomic processes in living cells.
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http://dx.doi.org/10.1002/anie.202014466 | DOI Listing |
ChemMedChem
December 2024
Universite de Dijon, Institut de Chimie Moleculaire, ICMUB CNRS UMR6302, 9, avenue Alain Savary, 21078, Dijon, FRANCE.
Fluorescence detection of DNA and RNA G-quadruplexes (G4s) is a very efficient strategy to assess not only the existence and prevalence of cellular G4s but also their relevance as targets for therapeutic interventions. Among the fluorophores used to this end, turn-on probes are the most interesting since their fluorescence is triggered only upon interaction with their G4 targets, which ensures a high sensitivity and selectivity of detection. We reported on a series of twice-as-smart G4 probes, which are both smart G4 ligands (whose structure is reorganized upon interaction with G4s) and smart fluorescent probes (whose fluorescence is turned on upon interaction with G4s).
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Université de Bordeaux, CBMN UMR5248, IECB, 2, rue Robert Escarpit, 33607, PESSAC, FRANCE.
Peptide stapling has emerged as a versatile approach in drug discovery to reinforce secondary structure elements especially α-helices and improve properties of linear bioactive peptides. Inspired by the prevalence of arginine in protein-protein and protein-DNA interfaces, we investigated guanidinium-stapling as a means to constrain helical peptides. Guanidinium stapling was readily achieved on solid support, utilizing two orthogonally protected lysine or unatural α-amino acid residues with an amino function.
View Article and Find Full Text PDFMikrochim Acta
December 2024
Key Laboratory for Analytical Science of Food Safety and Biology, MOE, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
A triple signal amplified electrochemical aptasensor for the detection of bisphenol A (BPA) was developed for the first time based on gold nanoparticles (AuNPs), hemin/G-quadruplex DNAzyme, and exonuclease I (Exo I) assisted amplification strategies. The BPA aptamer (Apt) hybridized with the capture probe (CP) was fixed on the gold electrode (GE) to form the double-stranded DNA (dsDNA) structure. When BPA was present, the Apt was detached from the GE surface by specific recognition between the BPA and Apt, forming BPA-Apt complexes in solution.
View Article and Find Full Text PDFMol Cancer
December 2024
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.
Extrachromosomal circular DNAs (eccDNAs) are a type of circular DNAs originating from but independent of chromosomal DNAs. Nowadays, with the rapid development of sequencing and bioinformatics, the accuracy of eccDNAs detection has significantly improved. This advancement has consequently enhanced the feasibility of exploring the biological characteristics and functions of eccDNAs.
View Article and Find Full Text PDFNat Commun
December 2024
Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression.
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