title: Identifying three-way DNA junction-specific small-molecules.
abstract: Three-way junction DNA (TWJ-DNA, also known as 3WJ-DNA) is an alternative secondary DNA structure comprised of three duplex-DNAs that converge towards a single point, termed the branch point. This point is characterized by unique geometrical properties that make its specific targeting by synthetic small-molecules possible. Such a targeting has already been demonstrated in the solid state but not thoroughly biophysically investigated in solution. Herein, a set of simple biophysical assays has been developed to identify TWJ-specific small-molecule ligands; these assays, inspired by the considerable body of work that has been reported to characterize the interactions between small-molecules and other higher-order DNA (notably quadruplex-DNA), have been calibrated with a known non-specific DNA binder (the porphyrin TMPyP4) and validated via the study of a small series of triazacyclononane (TACN) derivatives (metal-free or not) and the identification of a fairly-affinic and exquisitely TWJ-selective candidate (a TACN-quinoline construct named TACN-Q).
authors: Institut de Chimie Moléculaire de l'Université de Bourgogne, CNRS UMR5260, 9 Avenue Alain Savary, 21000 Dijon, France.
authors: Sophie
authors: S
authors: Vuong
authors: Loïc
authors: L
authors: Stefan
authors: Pauline
authors: P
authors: Lejault
authors: Yoann
authors: Y
authors: Rousselin
authors: Franck
authors: F
authors: Denat
authors: David
authors: D
authors: Monchaud
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D007700:Kinetics; D008024:Ligands; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism; D011166:Porphyrins / Q000138:chemical synthesis / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000378:metabolism; D012996:Solutions; D013057:Spectrum Analysis; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D001372:Aza Compounds; D008024:Ligands; D008670:Metals; D010880:Piperidines; D011166:Porphyrins; D011804:Quinolines; D054852:Small Molecule Libraries; D012996:Solutions; C482777:triazacyclononane; D004247:DNA