title: Bisintercalation of homodimeric thiazole orange dyes in DNA: effect of modifying the linker.
abstract: The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis[4-[3-methy l-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO) binds to double-stranded DNA (dsDNA) in a sequence selective bisintercalation. Each chromophore is sandwiched between two base pairs in a (5'-CpT-3'):(5'-ApG-3') site, and the linker spans over two base pairs in the minor groove. The binding of analogs of TOTO in which the linker has been modified is examined. The aim of the study is to utilize the sequence selectivity of the TOTO chromophores to enhance and/or alter the overall selectivity of the binding. One- and two-dimensional 1H-NMR investigations of complexes between TOTO analogs and various dsDNA oligonucleotides are reported. The following analogs were synthesized and used: 1,1'-(4,4,8,8-tetramethyl-4,8-diazadodecamethylene) -bis[4-[3-methyl-2,3-dihydro- (benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO10), 1,1'-(5,5,9,9-tetramethyl-5,9-diazatridecamethylene)-bis[4-[3-meth yl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO11), and 1,1'-(6,6,10,10-tetramethyl-6,10-diazapentadecamethylene)-bis[4-[3 -methyl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO13). The results show that with a longer linker the dyes can bisintercalate into two (5'-CpT-3'):(5'-ApG-3') sites separated by one or two base pairs. Bisintercalation in two such "isolated" binding sites yields non-nearest-neighbor bisintercalation in which the linker spans over more than two base pairs. The investigations also showed that an exact length of the linker is not crucial for the site selectivity since TOTO, TOTO10, and TOTO11 are almost equally suitable in binding selectively to the (5'CTAG-3')2 sequence. Fluorescence measurements show that TOTO10, TOTO11, and TOTO13 have higher fluorescence quantum yields than TOTO when bound to d(CGCTAGCG)2. This indicates that the length of the linker in TOTO may not be the optimum one in terms of using the dye as a fluorescence marker.
authors.affiliation: Department of Chemistry, Odense University, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Staerk
authors.forename: A A
authors.initials: AA
authors.lastname: Hamed
authors.forename: E B
authors.initials: EB
authors.lastname: Pedersen
authors.forename: J P
authors.initials: JP
authors.lastname: Jacobsen
mesh_terms: D052160:Benzothiazoles; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000138:chemical synthesis* / Q000378:metabolism; D019281:Dimerization; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011804:Quinolines; D011806:Quinolinium Compounds / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D018736:DNA Adducts; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D009841:Oligonucleotides; D011804:Quinolines; D011806:Quinolinium Compounds; D013844:Thiazoles; C051000:thiazole orange; C075295:1,1'-(4,4,7,7-tetramethyl-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-thiazole)-2-methylidene)quinolinium; D004247:DNA