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RESEARCH PRODUCT

Assessing the Differential Affinity of Small Molecules for Noncanonical DNA Structures

Loic StefanFranck DenatPierre Le GendrePhilippe RichardMichel PicquetBenoît BertrandDavid Monchaud

subject

Models MolecularBase pairBiologyG-quadruplex01 natural sciencesBiochemistrySmall Molecule Libraries03 medical and health scienceschemistry.chemical_compoundCaffeineFluorescence Resonance Energy TransferAnticarcinogenic AgentsMolecular BiologyComputingMilieux_MISCELLANEOUS030304 developmental biology0303 health sciencesBase Sequence010405 organic chemistryOrganic ChemistrySmall Molecule LibrariesDNAMolecular biologySmall molecule0104 chemical sciencesG-Quadruplexes[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/BiophysicsQuadruplex DNAFörster resonance energy transferchemistryDuplex (building)BiophysicsNucleic Acid ConformationThermodynamicsMolecular MedicineOrganogold CompoundsDNA

description

The targeting of higher-order DNA structures has been thoroughly developed with G-quadruplex DNA but not with other structures like branched DNA (also known as DNA junctions). Because these alternative higher-order DNA architectures might be of high biological relevance, we implemented a high-throughput version of the FRET melting assay that enabled us to map the interactions of a candidate with four different DNA structures (duplex- and quadruplex DNA, three- and four-way junctions) in a rapid and reliable manner. We also introduce a novel index, the BONDS (branched and other noncanonical DNA selectivity) index, to conveniently quantify this differential affinity.

https://doi.org/10.1002/cbic.201200396