[Dependence of mode of DNA binding to benzo crown derivatives of actinocin on the size and distance from the chromophore of crown fragments]. / Issledovanie zavisimosti sposoba sviazyvaniia s DNK benzokraunsoderzhashchikh proizvodnykh aktinotsina ot razmera i udalennosti ot khromofora kraun-gruppirovok.

Complexes of DNA with benzocrown derivatives of actinocin were studied by viscometry and dynamic birefringence. Changes in the macromolecular structure of DNA caused by complex formation were determined. Models of DNA binding to the studied compounds were suggested on the basis of data obtained. The intercalation of actinocin chromophore of benzocrown derivatives of actinocin was shown to occur only when benzocrown groups were bound to the chromophore via glycine fragment. A change in the distance between the crown group and the chromophore prevents ligand intercalation. Increase in medium ionic strength results in appearance of new nonintercalational binding mode for crown-containing compounds with DNA caused by interaction of the crown groups with DNA.

[Effect of a substituent origin in actinocin amides on their binding to DNA]. / Vliianie prirody zamestitelei amidov aktinotsina na sposob ikh sviazyvaniia s DNK.

The results of studies on the structure of complexes of DNA with compounds based on the actinocin chromophore, a center of binding of the antitumor antibiotic actinomycin D to DNA, were analyzed. In positions 1 and 9 of the chromophore of these compounds, pentapeptide lact ones of actinomycin D are replaced by groups of various origin. By using spectral, optical, and hydrodynamic methods a model of binding to DNA for each compound was constructed, and some regularities of complex formation depending on the structure of actinocin substituents and the amount of ligands in the complex were revealed.

[Interactions of DNA with ampholytes based on actinocin]. / Vzaimodeistvie DNK s amfolitami na osnove aktinosina.

The interaction of DNA with actinocin monoamides containing a substitute with the cationoide center in one of the amide groups were studied by spectrophotometry, induced circular dichroism, viscometry and flow birefringence methods. At pH values of solution exceeding their isoelectric point, these substances, which are in nature ampholytes, occur as zwitterions. At lover pH values they occur in the cationoid form. The constants of binding of these compounds to DNA were determined, and changes in DNA macromolecular structure caused by complexation were revealed. Models for the binding of these compounds to DNA were advanced. It was shown that compounds in the zwitterion form do not intercalate into the DNA double helix. The mode of binding of compounds to DNA in the cationoid form depends on the position of the cationoid center within the chromophore actinocin. Circular dichroism spectra of actinocyn-based ampholytes that bind to DNA in a different manner were obtained.

[Interaction of DNA with benzocrown derivatives of actinocin]. / Vzaimodeistvie DNK s benzokraun-proizvodnymi aktinotsina.

Complexes of DNA with actinocin derivatives containing benzocrown groups at the 1 and/or 9 positions of the chromophore were studied by spectrophotometric titration and circular dichroism. The actinocin chromophore and the crown fragments are the binding sites of the ligands with DNA. The mode of ligand-DNA binding is shown to depend on the size of the crown group, its distance to the actinocin chromophore, and the ionic strength of the medium. Selective toward Na+ ion benzocrown fragments combine with DNA phosphate groups. The simultaneous interaction of the actinocin chromophore with the DNA bases is possible only at optimal distance between both the binding sites of ligand molecule.

[Interaction of DNA with actinocyl-bis-thiazole]. / Vzaimodeistvie DNK s aktinoatsil-bis-bitiazolom.

The DNA complexes with actinocyl-bis-bithiazole have been investigated by spectrophotometry, viscometry and flow birefringence. It was estimated, that at low degrees of binding (r < or = 0.07) this compound binds to DNA by bisintercalation via bithiazole groups located in positions 1 and 9 of the phenoxazone chromophore. The phenoxazone moiety plays in this case the role of a link connecting two intercalating fragments. As r increases, external groove binding becomes the second type of complex formation.

[DNA interaction with the bifunctional acridine dye]. / Vzaimodeistvie DNK s bifunktsional'nym akridinovym krasitelem.

The comparative studies of the formation of DNA-complexes with the acridines containing one and two chromophores were accomplished. It was shown that both of acridines were bonded with DNA by means of intercalation irrespective of the ionic strength of medium (mu). When mu = 0.1 the diacridine (1,6-bis(9-acridylamino)-hexan) behaves as an mono-intercalator. Under these conditions both of the ligands exert equal influence of the molecular parameters of DNA. When mu = 0.001 the binding mode of the diacridine with DNA depends on its concentration in a complex. If a number of diacridine molecules on a pair of nucleotides (r) falls in a region 0 less than r less than 0.2 its binding with DNA is accomplished via the bis-intercalation mode and accompanied by the structure distortion of the monomer remnant of the macromolecule. As r increases from 0.2 to 0.4 the gradual change of the binding mode of the diacridine with DNA from bis-intercalation to mono-intercalation takes place. Moreover the structure of nucleotides is reduced. When mu = 0.001 the behaviour of DNA complexes with mono-acridine is analogous to the observed one when mu = 0.1.

[DNA interaction with low molecular weight ligands of different structure. III. DNA complexes with distactins]. / Vzaimodeistvie DNK s nizkomolekuliarnymi ligandami razlichnoi struktury. III. Kompleksy DNK s distaktsinami.

The DNA complexes with distactins have been investigated by means of spectrophotometry, viscosimetry and flow birefringence methods. The distactins are actinocin's derivatives containing in the 1,9 positions of the phenoxazone moiety oligopyrrolcarboxamide groups (like those of distamycin A), which have from one to three fragments of 1-methyl-4-amino-2-pyrrolic acid. The mode of DNA-distactins binding in water solution depends on the quantity of the methylpyrrole rings in the oligopeptide groups. The ligand with oligopeptide groups containing three methylpyrrole rings joins the DNA double helix only from outside by means of oligopeptide groups. The compounds with one and two methylpyrrole rings form two kinds of complexes with DNA: external binding and intercalation. In the latter case both chromophore and methylpyrrole fragments, interact with DNA.

[Comparative study of DNA interactions with daunomycin and proflavine in a solution]. / Sravnitel'noe issledovanie vzaimodeistviia DNK s daunomitsinom i proflavinom v rastvore.

The comparative investigations of DNA complexes with daunomycin and proflavine were proceeded by the technique of spectrophotometry, viscometry and flow birefringence for two ionic strengths of environment (mu). According to the spectrophotometry data there is an unique type of ligand binding with DNA for mu = 0.1. The intrinsic viscosity and optical anisotropy of DNA-daunomycin complex increase nonlinearly together with its equilibrium rigidity as the amount of the binding ligand (r) rises, contrary to the behaviour of the same characteristics of DNA-proflavine complexes. The discussion of the experimental data within a scope of different models of binding reveals the best agreement with the intercalation model. Evaluation of the angels between the orientation planes of chromophore and aminoglucose residue of a daunomycin molecule and the axis of DNA double-helix was performed. Apart from intercalation there is a process of external binding of daunomycin with DNA in the low ionic strength (mu = 0.001) solutions which arises mainly at higher values of r. This type of binding weakens the long-range electrostatic interactions (and also to a certain extent the short-range ones) in DNA chain that determine the behaviour of the parameters under study.

[DNA interaction with low molecular ligands of different structure. II. Complexes of DNA with actinomine and its analogs]. / Vzaimnodeistvie DNK s nizkomolekuliarnymi ligandami razlichnoi struktury. II. Kompleksy DNK s aktinominom i ego analogami.

DNA-complexes with actinomine and its analogues containing omega-dialkylaminoalkyl groups at 1,9 positions of the phenoxazone moiety were studied by technique of spectrophotometry, viscometry and flow birefringence. In the process of spectrophotometry titration two groups of spectra corresponding to different DNA--ligand ratio in a complex were observed. According to the experimental data the investigated compounds are bounded to DNA by means of intercalation and external binding. There within a region of low degrees of binding the intercalation type of the ligand--DNA interaction prevails. In virtue of the spectrophotometry data the intercalation binding share was calculated. The intrinsic viscosity of a complex increases in the case of ligand intercalation and does not change as it joins to the DNA double-helix from outside. Optical anisotropy of DNA molecule increases linearly irrespective of the way of ligand binding. Data on the flow birefringence permits to conclude that under external binding the angle between the normal to the ligand chromophore plane and the axis of DNA double-helix is about zero. During ligand intercalation the equilibrium rigidity of DNA molecules increases.

[Interactinos of DNA with low molecular weight ligands of various structures. I. Complexes of DNA with actinomycin and its simple analogs]. / Izuchenie vzaimodeistviia DNK s nizomolekuliarnymi ligandami razlichnoi struktury. I. Kompleksy DNK s aktinomitsinom i ego prostymi analogami.

The DNA complexes with actinomycin D and its simple analogues have been investigated by means of spectrophotometry, viscometry and flow birefringence methods. The number of binding sites per base pair of ligand on DNA depends on the nature of substitute in 1.9 position of the phenoxasone chromophore. It has been shown that phenoxasone derivatives without aminogroup in 2 position complex with DNA as in the case of simple actinomycin analogues. The intrinsic viscosity and optical anisotropy of DNA-analogues complexes increase linerly with increasing quantity of bound ligand. This testifies that the binding of the compounds under investigation to DNA molecule is of intercalation type. The character of variation of hydrodynamical and optical parameters of DNA molecule by its binding with actinomycin differs qualitatively from that observed by the binding with analogues. The experimental data obtained for DNA-actinomycin complexes can be interpreted only by suggesting a specific secondary structure alteration of the DNA molecule. It has been shown that the simple actinomycin analogues can not be used as an appropriate model for investigation of DNA-actinomycin complexes structure.

[The effect of acridine dyes on the molecular structure of DNA]. / Issledovanie vliianiia akridinovykh krasitelei na molekuliarnuiu strukturu DNK

DNA--acriflavin complexes have been investigated by the methods of flow birefringence and viscometry. The intrinsic viscosity and the optic anysotropy of the complex increase with the increasing quantities of binding dye. Experimental data are treated on the basis of different models of binding. At high ionic strength (mu = 0,1) one type of binding takes place which is described by the intercalation model. In this case the thermodynamic rigidity of DNA-molecule within the complex is proportional to "r". In solutions of low ionic strength (mu = 0,001), two types of DNA-acriflavin binding occur: intercalation and external binding. At low ionic strength, the spectrophotometric titration technique is shown to give a reduced value of "r".