[Hairpin oligonucleotides as actinomycin carriers].

The redistribution of actinomycin from hairpin oligonucleotide HP1 to dissolved DNA and DNA inside the cell has been discovered and investigated. It was found that the penetration of the antibiotic in a complex with HP1 into cancer cells takes place more effectively than that of the antibiotic separately. It is suggested that hairpin oligonucleotides can serve as molecular carriers of heterocyclic antibiotics to cancer cells.

Structural and thermodynamic features of complexes formed by DNA and synthetic polynucleotides with dodecylamine and dodecyltrimethylammonium bromide.

Complex formation of native and denatured DNA, single-stranded polyribonucleotides poly(A) and poly(U), as well as double-stranded poly(A).poly(U) with dodecylamine (DDA) and dodecyltrimethylammonium bromide (DTAB) has been studied by UV-, CD-, IR-spectroscopy and fluorescence analysis of hydrophobic probe pyrene. DDA and DTAB were shown to bind cooperatively with DNA and polyribonucleotides, resulting in the formation of complexes containing hydrophobic micelle-like clusters. Critical aggregation concentration (CAC) of DDA and DTAB shifts sharply to lower values (30-50 times) in the presence of DNA and polynucleotides as compared to critical micelle concentration (CMC) of free DDA and DTAB in solution. The analysis of binding isotherms within the frame of the model of cooperative binding of low-molecular ligands to linear polymers allowed us to determine the thermodynamic parameters of complex formation and estimate the contribution of electrostatic interaction of positively charged heads of amphiphiles with negatively charged phosphate groups of DNA and polyribonucleotides, and hydrophobic interaction of aliphatic chains to complex stability. Electrostatic interaction was shown to make the main contribution to the stability of DNA complexes with DDA, while preferential contribution of hydrophobic interactions is characteristic of DTAB complexes with DNA. The opposite effect of DDA and DTAB on the thermal stability of DNA double helix was demonstrated from UV-melting of DNA-while DTAB stabilizes the DNA helix, DDA, to the contrary, destabilizes it. The destabilizing effect of DDA seems to originate from the displacement of intramolecular hydrogen bonds in complementary Watson-Crick A.T and G.C base pairs with intermolecular H-bonds between unsubstituted DDA amino groups and proton-accepting sites of nucleic bases.

[Non stacking binding of 7-amino-actinomycin D and actinomycin D to DNA and model nucleotide systems in solutions]. / Nestékingovoe sviazyvanie 7-amino-aktinomitsina D i aktinomitsina D s DNK i model'nymi nukleotidnymi sistemami v rastvorakh.

Mechanism of actinomycin D (AMD) and 7-aminoactinomycin D (7AAMD) interaction with DNA and model nucleotide compounds was studied by absorption and fluorescence spectroscopy (steady-state, phase-modulation, and polarization). It was shown that complex formation does not result in energy transfer from photoexcited nucleotides to phenoxazone chromophore of 7AAMD that indicates the absence of stacking-like intercalation. This fact is fundamentally important to explain the biological effect of actinomycin on cells. It was revealed a fundamental difference in the complex-forming properties of AMD and 7AAMD. Thus AMD is capable of binding to guanine micelles to destroy them. 7AAMD forms complexes neither guanine micelles nor polyguanilic acid. 7AAMD binding sites on DNA can differ substantially from AMD binding sites. However, a strong competition is observed between AMD and 7AAMD for binding site in oligonucleotide HP1 used as DNA hairpin model. The efficient diameters of 7AAMD-HP1 complex and free 7AAMD were determined using the Levshin-Perren equation.

[Formation of DNA complexes with actinomycins in aqueous solutions and films]. / Formirovanie kompleksov DNK s aktinomitsinami v vodnykh rastvorakh i plenkakh.

The mechanisms of DNA interaction with actinomycin D (AMD), 7-amino-actinomycin D (7-AAMD), and ethidium bromide (EtBr) were studied in aqueous solutions and in condensed state (films coating plates). The use of the methods of absorption (UV, IR, and visible spectral ranges) and fluorescence (steady-state, polarization, and phase-modulation) spectroscopy revealed that (1) the formation of DNA complexes with 7-AAMD in solution was not accompanied by energy transfer from photoexcited nucleotides to phenoxazone chromophore and (2) the mechanism of ligand incorporation was distinct from stacking. In the film of the DNA-7-AAMD complex, which simulated the native state in a biological cell, the efficiency of the energy transfer was high. This indicates that a stacking-type mechanism underlies actinomycin intercalation into DNA. In the presence of high concentrations of 7-AAMD in the film, DNA denatured and its double-helical structure, degraded. In the DNA-AMD complex, the native B-form of DNA molecule was conserved both in films and in solution.