[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 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.

[Biochemical bases of adverse reactions to antibacterial preparations used in renal tuberculosis and means of their prevention]. / Nekotorye biokhimicheskie osnovy pobochnykh reaktsii na antibakterial'nye preparaty pri nefrotuberkuleze i puti ikh profilaktiki.

Factors leading to development of adverse reactions to antituberculous drugs in patients with nephrophthisis were studied and complex treatment regimens to prevent the reactions were developed. The use of such regimens along with chemotherapy allowed the frequency of adverse reactions to be lowered almost 2-fold in patients with limited nephrophthises and to postpone the development of adverse reactions in patients with extended tuberculosis for 1-1.5 months.

[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.

[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".