[Molecular dynamics simulation of the tubulin dimer with cytostatics].

Colchicin, podophylotoxin and indibulin are natural cytostatics that are used in the treatment of neoplasms. But applications of those compounds are rather restricted due to the high toxicity and low specificity. It seems very promising to investigate possibility to design new analogs of the above mentioned drugs that will possess higher cytostatic activity and less toxicity. For this purpose we see computer modeling experiments of tubulin and above mentioned compounds interaction as a powerful approach to design new artificial cytostatics with desired properties. In the current study the CHARMM software of protein-ligand interaction molecular dynamics method has been used. Particularly the following strategy has been applied. Molecules of the cytostatits have been positioned at several random positions around binding sites of tubulin and after energy minimization several binding sites have been identified on the tubulin macromolecule. In these binding sites structural changes that may be responsible for tubulin polymerization have been detected.

[Purification of enolase and phosphoglycerate mutase from human brain and formation of a bienzymatic complex from them]. / Ochistka enolazy i fosfoglitseratmutazy iz mozga cheloveka i formirovanie iz nik bifermentnogo kompleksa.

Neuron-specific enolase and phosphoglycerate mutase with specific activities of 106 and 215 U/mg, respectively, have been purified from human brain. Hydrophobic chromatography for enolase and blue Sepharose affinity chromatography for phosphoglycerate mutase were used as the last steps of purification. A heterobifunctional complex with fully preserved enolase and phosphoglycerate mutase activities was synthesized with the use of a bifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)propionate. Autoantibodies to the conjugate will be used for identifying the bienzymatic complex in vivo.

[Regulation of the activity of neuron-specific enolase by certain endogenous compounds]. / Reguliatsiia aktivnost neironspetsificheskoi enolazy nekotorymi éndogennymi soedineniiami.

The effects of glycolysis metabolites and some amino acids on the activity of bovine brain enolase have been studied. The inhibiting effect of glycolysis metabolites, of which two (2-phosphoglycolate and glyceraldehyde 3-phosphate) may be functionally significant, has been demonstrated. The action mechanisms of these compounds within a range of physiological concentrations as well as the combined effect of glyceraldehyde 3-phosphate and phosphoglyceromutase on enolase activity have been investigated.

[Modifying action of estradiol and progesterone on epileptic activity of the rat brain]. / Modifitsiruiushchee deistvie éstradiola i progesterona na épilepticheskuiu aktivnost' golovnogo mozga krys.

The effect of estradiol and progesterone on the activity of 3 regulatory enzymes of glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) in the brain of female rats was studied in the initial phase of hormonal action. Steroids were capable of modifying epileptic activity caused by pentetrazol, the action of estradiol being epileptogenic, that of progesterone anticonvulsant. Hormone action modifying epileptic activity, probably results from changes in intracellular metabolism and from changes in electrogenesis of nerve cells, the second mechanism being predominant.

[Relation between hormonal induction of enzymes regulating glycolysis and convulsive activity in the brain]. / O vzaimosviazi gormonal'noi induktsii reguliatornykh fermentov glikoliza i sudorozhnoi aktivnosti golovnogo mozga.

The authors have demonstrated the estradiol induction of the key glycolytic enzymes of the brain (hexokinase, phosphofructokinase and pyruvate kinase) which is "switched off" by injection of actinomycin-D--an inhibitor of protein biosynthesis. Another steroid hormone, progesterone, has an inhibitory action on the above enzymes. Administration of estradiol to rats significantly elevates the amplitude and frequency of contractility induced in them, while the same doses of progesterone decrease them. Thus, there is a definite correlation between the induction of glycolytic enzymes and sensitivity toward contractility on the one hand and the estradiol/progesterone ratio on the other. It is possible that activation of glycolysis may reduce the threshold of epileptic attacks providing an additional energy for epileptic manifestations.

[Various functional characteristics of enolase isoenzymes in mammals]. / Nekotorye funktsional'nye kharakteristiki izofermentov enolazy mlekopitaiushchikh.

Considerable stability of beta beta- (muscular) and gamma gamma- (neurospecific) forms to the denaturing influence of neutral salts of alkali metals is shown on purified isoenzymes (alpha alpha-, beta beta-, gamma gamma-forms) of beef brain and rabbit muscle. The rate of influence of these salts on the enzymic activity of the mentioned isoenzymes corresponds to the "lyotropic" series. Km of alpha alpha- and gamma gamma-isoenzymes are determined for 2-phosphoglycerate and phosphoenolpyruvate. It is found that alpha alpha-isoenzyme has larger affinity to phosphoenolpyruvate than gamma gamma-isoenzyme and it appears to play an essential role in participation of the given isoenzymes in the glycolysis and glyconeogenesis processes.

[Organ specific water-soluble cerebral cortex proteins; possible participation in physiological functions and pathologic manifestations]. / Organospetsificheskie vodorastvorimye belki kory golovnogo mozga; vozmozhnoe uchastie v fiziologicheskikh funktsiiakh i patologicheskikh proiavleniiakh.

The spectre of active antigens in brain is studied. The presence of 3 protein and 3 glycoprotein brain specific antigens is demonstrated. The possible participation of brain specific antigens in increased antibody formation in schizophrenics, multiple sclerosis and lateral ammiotrophic sclerosis is studied. The data obtained indicate the role of brain specific antigens to autoimmunity in those patients. The possible participation of one of the specific antigens of the brain, sialoglycoprotein GP-350, in physiological processes connected with the mechanism of memory is also studied. In experiments of inbred trained rats an activation of the synthesis of GP-350 is observed.

[Nucleic acid concentration in the brains of inbred rats of different strains]. / Soderzhanie nukleinovykh kislot v mozge inbrednykh krys razlichnykh linii.

The changes of nucleic acids content in the formation of conditioned skin-defence reflex was studied on inbred rats of various strains. In WGA rats the reflex was formed on the average aight stimulations. An increased RNA content was discovered by cytophotometric determination of the nucleic acids content in the neurons and perineural glia of the cerebral cortex in August rats only. It is assumed that an increased RNA synthesis in the animals of this strain can serve as the basis for their better training.