Lantushenko A. Effect of side chains of aromatic ligands on their association and competitive binding with a DNA oligomer

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0403U002393

Applicant for

Specialization

  • 03.00.02 - Біофізика

13-06-2003

Specialized Academic Board

Д 64.051.13

V.N. Karazin Kharkiv National University

Essay

Object of research - self- and hetero-association of series of synthetic phenoxazone compounds - analogues of antitumour antibiotic actinomycin D, phenanthridine dyes, antitumour anthracycline antibiotic daunomycin and deoxytetranucleotide 5'-d(TpGpCpA). Complexation and competitive binding of phenanthridine dyes and daunomycin with DNA in aqueous solution. Molecular mechanism of solubilization action of caffeine and nicotinamide on phenoxazone compound and riboflavin-mononucleotide. The purpose of work - establishment of influence of structural features of side chains of aromatic compounds with different medical-biological properties on physical-chemical parameters of their association in aqueous solution and competitive binding of ligands with DNA; finding out of the molecular mechanism of action of hydrotropic agents nicotinamide and caffeine on aromatic compounds. Methods of research - one- and two-dimensional homonuclear 1H NMR-spectroscopy (500 МHz), flow cytometry, and spectrophotometry. The structural and thermodynamic parameters of self-association of ethidium bromide, mono- and diazide ethidium and their hetero-association with antibiotic daunomycin have been received. The most probable spatial structures of complexes in aqueous solution are determined. The nature of physical interactions responsible for the stabilization of the complexes is established. Analysis of influence of structure of side chains of dyes on hetero-association and competitive binding of azido-analogues of ethidium and daunomycin with DNA oligomer has been made. The obtained results deepen existing representations about physical mechanisms of interaction of aromatic molecules among themselves and with DNA in multicomponent solution, that is important for prediction medical-biological properties of antibiotics, for purposeful synthesis of new compounds and increase of efficiency of medical-biological use of low soluble aromatic compounds.

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