Study of the complex formation of daunomycin with deoxytetranucleotides with bases of differing sequence in an aqueous solution by 1H-NMR spectroscopy

The complex formation of the antibiotic daunomycin with deoxytetranucleotides of different base sequence in the chain, 5'-d(GpCpGpC), 5'-d(CpGpCpG), and 5'-d(TpGpCpA) in aqueous salt solution was studied by 1D and 2D (2M-TOCSY and 2M-NOESY) 1H-NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts of molecules were measured. Based on these dependences, reaction equilibrium constants, relative content of various complexes depending on concentration and temperature, limiting values of chemical shifts of protons of daunomycin incorporated in various complexes, and the thermodynamic parameters delta H and delta S of complex formation were calculated. The analysis of the results enables the conclusion that the sites of predominant intercalation of daunomycin are triplet nucleotide sequences, the binding sites of the antibiotic with three consecutive GC pairs in the tetranucleotide duplex being more preferential. Daunomycin exhibits no sequence specificity upon binding to the single-stranded deoxynucleotide sequence. From the calculated values of induced chemical shifts of daunomycin protons and 2M-NOE data, the most probable spatial structures of complexes (1:2) of the antibiotic with deoxytetranucleotides were constructed. The binding of the second daunomycin molecule to both the single-stranded and duplex form of tetramers is of pronounced anticooperative mode, which is explained by the presence in the antibiotic of a positively charged amino sugar residue, which poses considerable steric constraints for the insertion of the second antibiotic molecule into the short tetranucleotide sequence. The results were compared with the data obtained under identical experimental conditions for typical intercalators proflavine and ethidium bromide.     

Relationships between hemorheology, erythrocyte metabolism, and von willebrand factor in athletes and patients with peripheral arterial disease

The relationship between hemorheology, erythrocyte ATP and 2,3-diphosphoglycerate (2,3-DPG) concentrations, and von Willebrand factor antigen was studied in athletes and peripheral arterial disease patients. Lower blood viscosity, mainly due to a higher erythrocyte deformability, was found in athletes compared to control subjects. Higher 2,3-DPG/Ht levels in athletes were correlated with blood viscosity, erythrocyte deformability, the rigidity index, and erythrocyte suspension viscosity at low shear stress. It is suggested that these relationships might be determined by the predominance of immature erythrocytes in the blood circulation of the athletes. In the group of patients, a decrease in ATP/Ht was related to increased erythrocyte aggregation and a higher erythrocyte suspension viscosity. Moreover, the concentration of von Willebrand factor was positively correlated with the erythrocyte aggregation index, erythrocyte suspension viscosity, and plasma viscosity. The results show that alterations in erythrocyte and plasma rheology may be involved in the modification of the functional state of the vascular endothelium and the development of atherosclerosis.     

Rheological Properties of Blood in Athletes

Rheological properties of blood were studied in subjects with high physical activity (athletes). It was found that the whole blood viscosity decreased under conditions of relative rest. The use of the concept of hemorheological profiles made it possible to reveal different profiles in subjects exposed to different courses of training exercise. The relationship between the rheological properties of blood and the total work capacity in humans was established. The typical parameter of profiles in subjects with high physical activity was high erythrocyte deformability associated mainly with erythrocyte form and viscoelastic properties of its membrane.     

Biochemical mechanisms of realization of antiviral and interferon-inducing activity of amixine and its analogs

Antiviral and interferon inducing activity of the amixine and its some derivatives, as well as their influence on the proteolytic enzymes activity, monooxygenase activity of the microsomal fraction, level of the lipids peroxidation were studied. Lack of correlation between antiviral and interferon inducing activity in the investigated series of compounds was found. Vice versa, the good correlation between interferon inducing activity and the elastase-like activities inhibition ability of the compounds was observed. It allows to state the assumption, that only one ability of compounds to induce of an interferon doesn't suffice for obtaining of high titres of interferon, and while their rather high antiproteolitic activity is necessary. It's shown, that except for one compound the influence of amixine and its derivatives on the red-ox enzymes activity well correlates with their ability to the interferon-inducing. All presented above allows to attribute amixine and its derivatives to polymodal antiviral agents.