[Design of transcription inhibitors on the basis of n-arylamides of 9-methyl- and 9-methoxyphenazine-1-carboxylic acids].

A convenient method of synthesis was developed and two series of N-arylamides of 9-methyl- and 9-methoxyphenazine-1-carboxylic acids were obtained. By the molecular docking method the mode of the synthesized compounds interaction with catalytic pocket of the RNA polymerase T7 transcription complex was simulated. Key ligand-receptor intermolecular contacts were identified. They are realized by various types of non-covalent interactions with line of conservative amino acid residues involved in recognition of incoming nucleotide, catalytic act of RNA synthesis as well as in stabilizing the RNA-DNA hybrid at early steps of transcription. In silico data indicate sufficient affinity of ligands for the receptor and allow to predict their ability to inhibit the functioning of RNA polymerase T7 transcription complex that is consistent with preliminary experimental results. Initial testing in a model RNA polymerase T7 transcription system demonstrates significant inhibition of in vitro RNA synthesis by investigated compounds at a concentration of 25 microg/ml (approximately 80 microM).

[New amides of phenazine-1-carboxylic acid: antimicrobial activity and structure-activity relationship].

Complex investigation of new phenazine-1-carboxylic acid (PCA-1) phenylamides allowed to reveal their ability for substantial growth retardation of three gram-positive bacterial strains--Micrococcus sp., Erysipelothrix rhusiopathiae and Staphylococcus aureus. The strong inhibitory activity of PCA-1 derivatives towards the RNA synthesis in in vitro T7-RNA-polymerase transcription system was also shown, and this property depended on concentration and structure of the tested compounds. The methods of computer modeling outlined the possible mechanism of RNA synthesis inhibition by PCA-1 amides: this process is arisen due to formation of stable complex of substances with enzyme at the position of substrate (rNTP) binding site. The revealed accordance of suppressor PCA-1 amides action in the enzymatic transcription system with antibacterial activity of these agents allows assuming that DNA-dependent RNA polymerase might be one of the cellular targets for tested bacteria. Such an approach permits to propose the use of such in vitro transcription model system to reveal biologically active substances among newly synthesized compounds, having close action mechanism.

[The development of a method for viral inactivation using thiophosphamide]. / Rozrobka sposobu inaktyvatsiï virusiv za dopomohoiu tiofosfamidu.

Using three-functional alkylating compound thiophosphamide complete inactivation of the influenza and herpesviruses of type 1 and 2 was achieved. The method provides full inactivation of DNA- and RNA-containing viruses and preservation of their immunogenic properties.

Mechanism of linear DNA circularization: formation of 'lasso'-like structures of pre-mRNA DNA copies.

An electron microscopic investigation of a DNA product synthesized on the pre-mRNA template using AMV reverse transcriptase in the absence of actinomycin D revealed linear single-stranded and double-stranded molecules, and, also, double-stranded branched as well as 'lasso'-like and circular structures. Models for the formation of such DNA structures are proposed.

[Use of wolfram trioxide for setting off preparations of nucleic acids]. / Primenenie trekhokisi vol'frama dlia otteneniia preparatov nukleinovykh kislot.

The use of tungsten trioxide for shadowing nucleic acids is shown to be possible. Approximately 20 mg of tungsten trioxide could be prepared by heating (25 s, 2 V) a coil (4 turns, 1.5 mm i.d.) made of tungsten wire 0.5 mm diameter in a vacuum evaporator at atmospheric pressure. As revealed by electron microscopy, this amount of tungsten trioxide is sufficient for qualitative rotary shadowing phage lambda DNA.

[Thermophilic and thermotolerant bacteria that assimilate methane]. / Termofil'nye i termotolerantnye bakterii, assimiliruiushchie metan

Microorganisms assimilating methane at temperatures above 40 degrees C were isolated from various natural sources: ooze, mud, waste water of coal pits. The bacteria are obligate methylotrophs and are represented by two groups: (a) thermotolerant, growing at 37 to 45 degrees C; and (b) thermophilic, growing at 50 to 62 degrees C. The selective factor used to isolate various physiological forms of methylotrophs is corresponding temperatures of growth which allow to isolate from the same substrate meso-, thermotolerant, and thermophilic forms. Morphological and physiological properties of the strains are described. The thermotolerant cultures of methylotrophs are similar to Methylobacter vinelandii, though differ from it by some characteristics. The thermophilic microorganisms should be classed as a separate species Methylococcus thermophilus.