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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

B - Z transition in poly (dG-dC) in the presence of mitoxantrone

Theoretical and experimental investigations show that depending on external medium conditions several ligands may bind to DNA by more than one modes (multimodal ligands) (Karapetyan et. al. 1996). Mitoxantrone (MTX) is one of the widely studied types of such ligands: depending on Na+ concentration, nucleotide sequences, ligands concentration MTX may bind with DNA by different mechanisms (Awasthi, Dogra & Barthwal, 2013). Despite of the existence in literature of large amount of reports the binding modes of MTX with the DNA must be subject to refinement. Moreover there has not yet any report about the interaction of MTX with Z-DNA.

We present here the results of circular dichroism (CD) studies on MTX binding to salt driven left-handed conformation of poly (dG- dC) (Pohl, Jovin an & Baehr, 1972). Obtained experimental data suggest that the increase of mitoxantrone concentration does not cause even slight changes on the CD spectra of Z-form of poly (dG-dC) which is the evidence of lack of interaction of MTX with the Z form of polymer.

In contrast with the ligands (EtBr) that bind with B-form DNA and obstacle B-Z transition at high concentrations of NaCl and ethanol (Karapetyan et al., 1989) despite of ligand concentration in solution, mitoxantrone interferes B-Z transition, but does not barrier the transitions process.

We are going to discuss the possible role of two distinct modes of MTX (partial stacking and external binding) interaction on the B-Z transition of DNA.

References
    P. Awasthi, Sh. Dogra & R. Barthwal. (2013). Multispectroscopic methods reveal different modes of interaction of anti cancer drug mitoxantrone with Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT), J. Photochem. Photobiol. B. 127, 78-87.

    A.T. Karapetian, N.M. Mehrabian, G.A. Terzikian, P.O. Vardevanian, A.P. Antonian, O.F. Borisova, M.D. Frank-Kamenetskii. (1996), Theoretical treatment of melting of complexes of DNA with ligands having several types of binding sites on helical and single-stranded DNA, Journal of Biomolecular Structure and Dynamics 14, 275-283.

    A.T.Karapetyan, E.E. Minyat, P.O. Vardevanyan, & V.l. Ivanov. (1989). Thermodynamics of B-Z Transition of Poly[d(G-C)] in a Water-Ethanol Solution. The Tie Calorimetry, Journal of Biomolecular Structure and Dynamics 6, 1233-1238.

    F.M. Pohl, T.M. Jovin, W. Baehr, JJ. Holbrook (1972), Ethidium bromide as a cooperative effector of a DNA structure, Proc. Nat. Acad. Sci. 69, 3805-09.


Armen T. Karapetyan
Margairta A.Torosyan
Yuri S. Babayan

Department of Physics and Electrical Engineering
National University of Architecture and Construction
Yerevan, 0009, Armenia

Ph: (+374 10) 54-74-25
Fx: (+374 10) 58-72-84
karapetyanat@gmail.com