[Study of the interaction of 2'-5'-oligoadenylates and their analogues with proteins by fluorescence spectroscopy].

The interaction of "core" 2'-5'-oligoadenylates (2-5A) and their analogues with proteins albumin, interferon and immunoglobulin G was studied by fluorescence spectroscopy methods. Strong quenching of protein fluorescence (up to 67%) was observed upon interaction of oligoadenylates in concentration of 5 x 10(-5) M with albumin. Investigated compounds quenched the emission of interferon to a lesser extent, whereas no significant fluorescence changes occurred upon interaction with immunoglobulin under the same conditions. The level of quenching depended on the structure of 2-5A compounds and decreased with the decrease of their concentration. These data suggest that 2-5A actively bind to albumin and less efficiently to interferon, and practically do not interact with immunoglobulin. Taking into consideration different efficiency of quenching of the fluorescence excited at 280 and 296 nm, the assumption has been made about a possible role of tyrosine and tryptophan in the binding of a given compound to proteins. Possible mechanisms of interaction of oligoadenylates with proteins are discussed.

[Effects of RNA on blood circulation and its adrenergic and cholinergic regulation].

Experimental investigations of the impacts of microRNA agent nucleks on heart function, coronary and systemic circulation as well as on adrenergic and cholinergic mechanisms of cardiohaemodynamics regulation were performed on anaesthetized dogs. Bolus injection (0.1-100.0 mg) or prolonged infusion (2.5 mg/min) of nucleks into perfusion coronary artery blood stream induced coronary dilatation. Under the intracoronary infusion of nucleks we observed more pronounced coronary vasodilatation and left ventricle pressure elevation in response to adrenergic heart receptors stimulation by norepinephrine (0.05-5.0 mkg, intracoronary). Besides that the drug infusion into coronary blood stream promoted the acceleration of recovery processes of the studied cardiohaemnodynamic parameters after norepinephrine injection. After intracoronary infusion of nucleks the sensitivity of cholinergic receptors to the stimulation by acetylcholine (0.001-1.0 mkg, intracoronary) increased significantly. After NO-synthase blockade (L-NAME, infusion 2.0 mg/min, intracoronary) nucleks did not cause any effect on coronary vessels tone and heart activity both it did not change their adrenergic and cholinergic reactivity.

[Hydrolysis and the products of 2',5'-oligoadenylate "core" cleavage]. / Vyvchennia hidrolizu i produktiv rozshcheplennia "koru" 2',5'-olihoadenilatu.

"Core" 2',5'-oligoadenylates resistance to the action of phosphodiesterases was investigated by HPLC and the method of capillary electrophoresis. Oligoadenylate hydrolysis followed by the formation of adenosine and AMP was shown both in the case of incubation with the cells lysate and with the snake venoms phosphodiesterase. Kinetics of products formation in the process of enzymatic hydrolysis was analysed. In contrast to HPLC the method of capillary electrophoresis was observed to be more efficient for 2',5'-oligoadenylates hydrolysis products cleavage. The substance under study was shown not to have sufficient resistance to the enzyme and the latter, probably, hampers its therapeutic use.