title: On the sequence selective bis-intercalation of a homodimeric thiazole orange dye in DNA.
abstract: The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4, 8-diazaundecamethylene)-bis-4-[(3-methyl-2,3-dihydro(benzo-1, 3-thiazolyl)-2-methylidene]quinolinium tetraiodide (TOTO) binds sequence selectively to double-stranded DNA (dsDNA) by bis-intercalation. Each chromophore is sandwiched between two base pairs in a d(5'-py-p-py-3'):d(5'-pu-p-pu-3') site, and the linker spans over two base pairs in the minor groove. We have examined the binding of TOTO to various dsDNA oligonucleotides containing variations of the 5'-CTAG-3' binding motif by introducing inosine (I = inosine, 2-desaminoguanosine) and 5-methylcytosine ((me)C). A one- and two-dimensional NMR spectroscopy characterization yielded detailed structural information on the binding mode and for the well-defined TOTO-complexes competition experiments allowed determination of the relative binding strengths resulting from the various structural alterations. The experimentally observed base pair preference of TOTO in the palindromic sequences investigated is (me)CG > CG > CI > TA for the flanking base pair and (me)CI > CI > TA > CG > UA for the central base pair. The best binding site observed so far is the d(5-C(me)CIG-3')(2) site. This site is much more favorable than the d(5'-CTAG-3')(2) site formerly believed to be the best binding site. The present paper discusses these results in terms of different contributions to the binding affinity and offers some explanations for the site selectivity of TOTO.
authors.affiliation: Department of Chemistry, Odense University, DK-5230 Odense M, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Bunkenborg
authors.forename: M M
authors.initials: MM
authors.lastname: Stidsen
authors.forename: J P
authors.initials: JP
authors.lastname: Jacobsen
mesh_terms: D044503:5-Methylcytosine; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D003432:Cross-Linking Reagents / Q000737:chemistry; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006151:Guanosine / Q000737:chemistry / Q000378:metabolism; D007288:Inosine / Q000737:chemistry / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D011806:Quinolinium Compounds / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D007364:Intercalating Agents; D011806:Quinolinium Compounds; C086329:TOTO-1 thiazole orange dye; D013844:Thiazoles; C117926:totoet; D006151:Guanosine; D007288:Inosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA