title: Exploring multiple binding sites of an indoloquinoline in triple-helical DNA: a paradigm for DNA triplex-selective intercalators.
abstract: Employing NMR spectroscopic methods preferred binding sites of a triplex-selective indoloquinoline drug were examined with three DNA triplex targets. To directly derive and evaluate number and type of the different sites of interaction, studies were performed on short triple-helical constructs specifically labeled with 3-(15)N thymidine probes. The detection and assignment of several coexisting species was enabled through the observation of slow exchange on the chemical shift timescale between complexes and free triplex. In general, the 5'-triplex-duplex junction constitutes the most favorable intercalation site, in particular when flanked by a TAT base triad. NMR data also revealed two different orientations for the intercalating indoloquinoline drug. Binding affinity significantly decreases with a C(+)GC triad bordering the junction but junction binding is still preferred over intercalation between TAT base triads within the triplex stem. In addition to the intercalation between two uncharged TAT triplets, intercalation between a TAT and a 3'-terminal C(+)GC triplet was also observed, indicating a non-protonated third strand cytosine at the triplex end position.
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dickerhoff
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.
authors.forename: Fanny
authors.initials: F
authors.lastname: Riechert-Krause
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Seifert
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany. Electronic address: weisz@uni-greifswald.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Weisz
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D011522:Protons; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism
chemical_list: C000599869:11-phenyl-10H-indolo(3,2-b)quinoline; D007211:Indoles; D007364:Intercalating Agents; D008024:Ligands; D009841:Oligonucleotides; D011522:Protons; D011804:Quinolines; C051802:triplex DNA; D004247:DNA
keywords: DNA triplex; Indoloquinoline; NMR; Triplex–duplex junction