Biopolym. Cell. 1999; 15(1):75-82.
Interaction of cyanine dyes with nucleic acids. 5. Towards model of «half intercalation of monomethyne cyanine dyes into double-stranded nucleic acids
1Yarmoluk S. M., 1Kovalska V. B., 2Kovtun Yu. P.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of organic chemistry NAS of Ukraine
    5, Murmanska Str., Kyiv, Ukraine, 02660


Recently we have proposed a model of "half intercalation" of monomethyne cyanine dye into the double-stranded helix. Benzothiazole terminal heterocycle «classically» intercalates, nestled between the adjacent base pairs just when second heterocycle is spatially fixed by nucleic acid groove. We consider that heterocycle with high basicity hits in the more nucleophilic groove whereat heterocycle with low basicity insert in more electrophilic interbase space. The purpose of this study is to determine the possible fixation mode of second heterocycle in nucleic acid groove. We synthesized and investigated the series of structure-like cyanine dyes which have different charge electronic distribution. We suppose that binding of second heterocycle of high basicity is caused by both spatial fixation and electrostatic interaction with phosphate group of nucleic acid. Monomethyne pyria'inium cyanine dye (Cyan 40; 4-((1-methyl-benzothiazoleilidene-2)methyl: 1,2,6-trimethylpyridinium p-toluenesulfonatc interacted with native DNA and RNA with strong fluorescence enhancement. It seems to be perspective for the development of new nucleic acid binding cyanine dyes.


[1] Gilden DH, Vafai A, Shtram Y, Becker Y, Devlin M, Wellish M. Varicella-zoster virus DNA in human sensory ganglia. Nature. 1983;306(5942):478-80.
[2] Fischer SG, Lerman LS. DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: correspondence with melting theory. Proc Natl Acad Sci USA. 1983;80(6):1579-83.
[3] Durst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA. 1983;80(12):3812-5.
[4] Ju J, Glazer AN, Mathies RA. Energy transfer primers: a new fluorescence labeling paradigm for DNA sequencing and analysis. Nat Med. 1996;2(2):246-9.
[5] Rye HS, Quesada MA, Peck K, Mathies RA, Glazer AN. High-sensitivity two-color detection of double-stranded DNA with a confocal fluorescence gel scanner using ethidium homodimer and thiazole orange. Nucleic Acids Res. 1991;19(2):327-33.
[6] Haughland R. P. Molecular probes. Handbook of fluorescent probes and research chemicals. Eugene, 1996. 679 p.
[7] Lee LG, Chen CH, Chiu LA. Thiazole orange: a new dye for reticulocyte analysis. Cytometry. 1986;7(6):508-17.
[8] Schwartz H. E., Ulfelder K. J. Capillary electrophoresis with laser-induced fluorescence detection of PCR fragments using thiazole orange. Anal. Chem., 1992, 64 (15), pp 1737–1740.
[9] Carlsson C, Larsson A, Jonsson M, Albinsson B, Norden B. Optical and Photophysical Properties of the Oxazole Yellow DNA Probes YO and YOYO. J. Phys. Chem., 1994, 98 (40), pp 10313–10321.
[10] Jacobsen JP, Pedersen JB, Hansen LF, Wemmer DE. Site selective bis-intercalation of a homodimeric thiazole orange dye in DNA oligonucleotides. Nucleic Acids Res. 1995;23(5):753-60.
[11] Rye HS, Glazer AN. Interaction of dimeric intercalating dyes with single-stranded DNA. Nucleic Acids Res. 1995;23(7):1215-22.
[12] Yarmoluk S. M., Kovalska V. B., Smirnova T. V., Shandura M. P., Kovtun Y. P., Matsuka G. Kh. IInteraction of cyanine dyes with nucleic acids. 2. Spectroscopic properties of methyleneoxy analogues of Thiazole Orange Biopolym. Cell. 1996; 12(6):74-81
[13] Hamer F. M. The cyanine dyes and related compounds. New York: J. Willey, 1964. 790 p.
[14] Rye HS, Yue S, Wemmer DE, Quesada MA, Haugland RP, Mathies RA, Glazer AN.Stable fluorescent complexes of double-stranded DNA with bis-intercalating asymmetric cyanine dyes: properties and applications. Nucleic Acids Res. 1992;20(11):2803-12.
[15] Herz A. H. Dye-dye interactions of cyanines in solution and at AgBr surfaces. Photogr. Sci. Eng. 1974. 18:323—335.
[16] Israelachvili J. Intermolecular and surface forces. San Diego: Acad, press, 1992:76—105, 122—133.
[17] Ishchenko A. A. Structure and spectroscopic properties of polymethyne cyanine dyes. Kyiv: Nauk. dumka 1994. 231 p.
[18] Larsson A, Carlsson C, Jonsson M, Albinsson B. Characterization of the Binding of the Fluorescent Dyes YO and YOYO to DNA by Polarized Light Spectroscopy. J. Am. Chem. Soc., 1994, 116 (19), pp 8459–8465
[19] Tyutyulkov N. Polymethine dyes — structures and proper ties. Sofia: St. Kliment Ohridski Univ. press, 1991:107—123.