Novel Phosphonium Dye TDV1 as a Potential Fluorescent Probe to Monitor DNA Interactions with Lysozyme Amyloid Fibrils

  • Olga Zhytniakivska Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • Uliana Tarabara Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • Kateryna Vus Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • Valeriya Trusova Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • Galyna Gorbenko Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • Nikolai Gadjev Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria
  • Todor Deligeorgiev Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria
Keywords: Phosphonium dye, fibrillar lysozyme, DNA, J-aggregates


The applicability of the novel cationic phosphonium dye TDV1 to monitor the complexation between DNA and pathologically aggregated proteins, amyloid fibrils, was tested using the optical spectroscopy and molecular docking techniques. TDV1 has been found to be highly emissive in buffer solution and is characterized by one well-defined fluorescence peak attributed to the dye monomers. The association of the dye with the double stranded DNA was followed by the enhancement of monomer fluorescence coupled with a bathochromic shift of the emission maximum. The addition of fibrillar lysozyme (LzF) to TDV1-DNA mixture led to the further enhancement of fluorescence intensity of the monomeric dye form coupled with a hypsochromic shift of the emission maximum and an appearance of a second long-wavelength peak. An assumption has been made that the fluorescence enhancement augmenting with increasing the protein concentration in the TDV1/DNA system is produced by the interaction of the free TDV1 monomers with lysozyme fibrils as well as by the LzF-induced conformational alterations of DNA. The long-wavelength peak emerging in the presence of LzF is presumably a consequence of the J-aggregate formation upon the TDV1 association with lysozyme fibrils. The molecular docking studies showed that TDV1 monomers are incorporated into the fibril grooves associating with 7 β-strands in such a way that the dye long axis is parallel to the fibril axis. The most energetically favorable position of TDV1 is the S60-W62/G54-L56 groove in the lysozyme fibril core. In contrast, the TDV1 dimers seem to associate with the more hydrophilic side of the model β-sheet. Cumulatively, the results from the absorption and fluorescence measurements, together with the molecular docking analysis are consistent with the minor groove mode of the TDV1 binding to dsDNA. The electrostatic interactions seem to play a predominant role in the TDV1 complexation with the double stranded DNA, while the hydrophobic interactions and steric hindrances are supposed to be influential in the association of TDV1 with fibrillar lysozyme.


Download data is not yet available.


E. Karran, M. Mercken and B. Strooper, Nature Reviews Drug Discovery, 10, 698–712 (2011), doi: 10.1038/nrd3505.

J. Adamcik and R. Mezzenga, Macromolecules, 45, 1137−1150 (2012), doi: 10.1021/ma202157h.

C.M. Dobson, Cold Spring Harb. Perspect. Biol. 9, 1-14 (2017), doi: 10.1101/cshperspect.a023648.

J. Diaz-Nido, F. Wandosell and J. Avila, Peptides. 23, 1323-1332 (2002), doi: 10.1016/S0196-9781(02)00068-2.

J. van Horssen, P. Wesseling, L.P. van den Heuvel, R.M. de Waal and M.M. Verbeek, Lancet. Neurol. 2(8), 482−492 (2003), doi: 10.1016/S1474-4422(03)00484-8.

J.B. Ancsin, Amyloid. 10, 67-79 (2003), doi: 10.3109/13506120309041728.

S.D. Ginsberg, J.E. Galvin, T.S Chiu, V.M. Lee, E. Masliah and J.Q. Trojanowski, Acta Neuropathol. 96(5), 487–494 (1998), doi: 10.1007/s004010050.

M.R. Deleault, R.W. Lucassen and S. Supattapone, Nature, 425, 717−720 (2003), doi: 10.1038/nature01979.

M. Hasegawa, R.A. Crowther, R. Gakes and M. Goedert, J. Biol. Chem. 272, 33118–33124 (1997), doi: 10.1074/jbc.272.52.33118.

T. Kampers, P. Friedhoff, J. Biernat, E.M. Mandelkow and E. Mandelkow, FEBS Lett. 399(3), 344–349 (1996), doi: 10.1016/S0014-5793(96)01386-5.

M.L. Hedge and K.S.J. Rao, Arch. Biochem. Biophys. 464(1), 57–69 (2007), doi: 10.1016/

D. Cherny, W. Hoyer, V. Subramaniam and T.M. Jovin, J. Mol. Biol. 344, 929–938 (2004), doi: 10.1016/j.jmb.2004.09.096.

M. Calamai, J.R. Kumita, J. Mifsud, C. Parrini, M. Ramazzotti, G. Ramponi, N. Taddei, F. Chiti and C. Dobson, Biochemistry. 45, 12806–12815 (2006), doi: 10.1021/bi0610653.

S. Ghosh, N.P. Pandey, S. Sen, D.R. Tripathy and S. Dasgupta, J. Photochem. Photobiol. B. 127, 52–60 (2013), doi: 10.1016/j.jphotobiol.2013.07.015.

J.D. Domizio, R. Thang, L.J. Stagg, M. Gagea, M. Zhuo, J.E. Ladbury and W. Cao, J. Biol. Chem. 287, 736–747 (2012), doi: 10.1074/jbc.M111.238477.

D.L. Lindberg and E.K. Esbjorner, Biochem. Biophys. Res. Commun. 469, 313–318 (2016), doi: 10.1016/j.bbrc.2015.11.051.

V.B. Kovalska, M.Y. Losytskyy, O.I. Tolmachev, Y.L. Slominskii, G.M. Segers-Nolten, V. Subramaniam and S.M. Yarmoluk, J. Fluoresc. 22, 1441–1448 (2012), doi: 10.1007/s10895-012-1081-x.

K.D. Volkova, V.B. Kovalska, A.O. Balanda, R.J. Vermeij, V. Subramaniam, Y.L. Slominskii and S.M. Yarmoluk, J. Biochem. Biophys. Meth. 70, 727–733 (2007), doi: 10.1016/j.jbbm.2007.03.008.

K.Vus, U. Tarabara, A. Kurutos, O. Ryzhova, G. Gorbenko, V. Trusova, N. Gadjev and T. Deligeorgiev, Mol. Biosyst. 13, 970–980 (2017), doi: 10.1039/c7mb00185a.

A. Kurutos, O. Ryzhova, U. Tarabara, V. Trusova, G. Gorbenko, N. Gadjev and T. Deligeorgiev, J. Photochem. Photobiol. A. 328, 87–96 (2016), doi: 10.1016/j.jphotochem.2016.05.019.

Q. Li, J.-S. Lee, C. Ha, C. B. Park, G. Yang, W. B. Gan and Y.-T. Chang, Angew. Chem. Int. Ed. 43(46), 6331–6335 (2004), doi: 10.1002/anie.200461600.

C.V. Kumar, R.S. Turner and E.H. Asuncion, J. Photochem. Photobiol. A. 74, 231–238 (1993), doi: 10.1016/1010-6030(93)80121-O.

J. Yan, J. Zhu, K. Zhou, J. Wang, H. Tan, Z. Xu, S. Chen, Y. Lu, M. Cui, L. Zhang, Chem. Comm. 53, 9910-9913 (2017), doi: 10.1039/C7CC05056A.

M.K. Johansson, H. Feedder, D. Dick, and R.M. Cook, J. Am. Chem. Soc. 124(24), 6950-6956 (2002), doi: 10.1021/ja025678o.

B. Birkan, D. Gulen and S. Ozcelic, J. Phys. Chem. 110, 10805-10813 (2006), doi: 10.1021/jp0573846.

M. Kasha, H.R. Rawls and M.A. El-Bayoumi, Pure. Appl. Chem. 100, 17287-17296 (1996).

K.S. Hannah and B.S. Armitage, Acc. Chem. Res. 37, 845-853 (2004), doi: 10.1021/ar030257c.

M. Wang, G. Silva and B. Armitage, J. Am. Chem. Soc. 122, 9977-9986 (2000), doi: 10.1021/ja002184n.

M.R. Smaoui, F. Poitevin, M. Delarue, P. Koehl, H. Orland, and J. Waldispühl, Biophys. J. 104(3), 683-693 (2013), doi: 10.1016/j.bpj.2012.12.037.

M.D. Hanwell, D.E. Curtis, D.C. Lonie, T. Vandermeerch, E. Zurek and G.R. Hutchison, J. Cheminform. 4, 17 (2012), doi: 10.1186/1758-2946-4-17.

T. Sarwar, S. Rehman, A.A. Husain, H.M. Ishqi and M. Tabish, Int. J. Biol. Macromol. 73. 9–16 (2015), doi: 10.1016/j.ijbiomac.2014.10.017.

J.L. Seifert, R.E. Connor, S.A. Kushon, M. Wang and B.A. Armitage, J. Am. Chem. Soc. 121, 2987–2995 (1999), doi: 10.1021/ja984279j.

D.E. Wemmer, Annu. Rev. Biophys. Biomol. Struct. 29, 439–461 (2000), doi: 10.1146/annurev.biophys.29.1.439.

T.Yu. Ogul’chansky, M.Yu. Losytsky, V.B. Kovalska, S.S. Lukashov, V.M. Yashcuk and S.M. Yarmoluk, Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 57, 2705–2715 (2001), doi: 10.1016/S1386-1425(01)00537-6.

G.Ya. Guralchuk, A.V. Sorokin, I.K. Katrunov, S.L. Yefimova, A.N. Lebedenko, Yu.V. Malyukin and S.M. Yarmoluk, J. Fluoresc. 17, 370–376 (2007), doi: 10.1007/s10895-007-0201-5.

H. von Berlepsch, C. Böttcher, A. Ouart, C. Burger, S. Dähne, S. Kirstein, J. Phys. Chem. B. 104(22), 5255-5262 (2000), doi: 10.1021/jp000220z.

S. Spano, Acc. Chem. Res. 43(3), 429-439 (2010), doi: 10.1021/ar900233v.

T. Stokke and T. Steen, J. Histochem. Cytochem. 33(4), 333-338 (1985). doi: 10.1177/33.4.2579998.

J. Kapuscinski, Z. Darzynkiewicz and M.R. Melamed, Biochem. Pharm. 32(24), 3679-3694 (1983).

S.M. Yarmoluk, S.S. Lukashov, T.Yu. Ogul’chansky, M.Yu. Losytskyy and O.S. Kornyushyna, Biopolymers. 62, 219–227 (2001).

P. Hanczyc, L. Sznitko, C. Zhong and A. Heeger, ACS Photonics. 2(12), 1755–1762 (2015), doi: 10.1021/acsphotonics.5b00458.

K.D. Volkova, V.B. Kovalska, M.Y. Losytskyy, K.O. Fal, N.O. Derevyanko, Y.L. Slominskii, O.I. Tolmachov and S.M. Yarmoluk, J. Fluoresc. 21, 775–784 (2011), doi: 10.1007/s10895-010-0770-6.

M. Groenning, M. Norrman, J. Flink, M. Weert, J. Bukrinsky, G. Schluckebier and S. Frokjaer, J. Struct. Biol. 159(3), 483-497 (2007), doi: 10.1016/j.jsb.2007.06.004.

M.R.H. Krebs, E.H. C. Bromley and A.M. Donald, J. Struct. Biol. 149, 30-37 (2005), doi: 10.1016/j.jsb.2004.08.002.

K.Vus, V. Trusova, G. Gorbenko, R. Sood, E. Kirilova, G. Kirilov, I. Kalnina and P. Kinnunen, J. Fluoresc. 24, 493–504 (2014), doi: 10.1007/s10895-013-1318-3.

F.A. Schaberle, V.A. Kuz’min, and I.E. Borissevitch, Biochim. Biophys. Acta. 1621, 183–191 (2003), doi: 10.1016/S0304-4165(03)00057-6.

0 article
How to Cite
Zhytniakivska, O., Tarabara, U., Vus, K., Trusova, V., Gorbenko, G., Gadjev, N., & Deligeorgiev, T. (2019). Novel Phosphonium Dye TDV1 as a Potential Fluorescent Probe to Monitor DNA Interactions with Lysozyme Amyloid Fibrils. East European Journal of Physics, (2), 19-26.