Scientific achievements and developments

– The new biophysical mechanism of regulating the proteome activity under normal condition and under pathology realized by transforming a structural-dynamic state of proteins against the background of their structure constancy was established;
– The scheme of interrelation between internal dynamics, conformation, and functional activity of the protein was proposed. It was established that gradual changes in the protein activity are achieved by the shifts of internal dynamics and the possibility of gradual regulation of protein function is provided by the conformational transitions. The existence of optimal amplitude and frequency of equilibrium motions of protein structural elements for protein functioning was shown;
– The fluctuation model of enzyme-substrate interactions was proposed. In contrast to generally accepted models of “key-lock” by Fisher and “induced correspondence” by Koshland, the fluctuation model is based on taking into consideration the role of the protein internal dynamics in the processes of substrate binding by the active site of the enzyme, destabilization of covalent bonds of substrate and release of reaction products;
– New mechanisms of ion strength and pH action on enzyme activity realized by the shifts in protein slow internal dynamics were detected;
– The conception about the ability of proteins to exist in several thermodynamically stable and partially folded states differing in amplitudes of structural transformations and the modification degree of functional activity was stated and experimentally substantiated;
-New method to study the slow (millisecond) internal dynamics of membrane protein structure in situ was developed. The method is based on the recording of parameters of tryptophane phosphorescence at room temperature of proteins;
– Contrasting differences in slow internal dynamics of peripheral and integral membrane proteins of erythrocyte membranes in situ were detected. The effect of protein-protein and protein-lipid interactions on slow internal dynamics of membrane protein structure was revealed. The possibility of physical and chemical factors and agents to modify the slow internal dynamics of membrane proteins in human erythrocytes was revealed;
– It was shown that limited slow internal dynamics of membrane proteins as compared with the majority of water-soluble proteins is caused by the presence of protein ensembles in the membrane, isolation of macromolecules from aqueous surroundings in lipid bilayer composition and by a high content of α-helices and β-sheets in macromolecules;
– It was shown that changes in the slow internal dynamics of proteins along with their conformational rearrangements play an important role in the processes of intracellular signaling and transformation of external signals to the cell functional response;
– The relation was revealed between the changes in the slow internal dynamics of membrane proteins and the development of pathology. The changes in the structural and dynamic state of lymphocyte membrane proteins of patients with oncological and autoimmune diseases were revealed. It was shown that aggregation of proteins of cataract crystalline lens tissues is associated with a rise in inflexibility of macromolecule structure;
– The new method for analysis lipid peroxidation products in the biological membranes in situ was developed. The method is based on recording spectral and kinetic phosphorescence parameters of lipid peroxidation products at room temperature;
-Inhibitory analysis of thrombin, trypsin, and α-chymotrypsin action at their low concentrations on aggregation activity of platelets under conditions of blocking phospholipase C, cyclooxygenase, lipoxygenase, and calmodulin-dependent enzymes was carried out. It was shown that products of phosphoinositides hydrolysis and arachidonic acid metabolism are involved in processes of platelets aggregation under the action of proteolytic enzymes;
– It was found that the ability to protease-induced platelet aggregation in pregnant women with preeclampsia decreases compared with an uncomplicated pregnancy;
– Biophysical mechanisms of the interaction of dendrimers with proteins have been established. It was shown that dendrimer – protein binding occurs mainly on the surface of the protein globule and is determined by electrostatic interactions between charged dendrimer groups and amino acid residues of the protein. Depending on the nature of the protein macromolecule, the interaction affects the secondary structure of the protein, can change its conformation and intramolecular;
– It has been shown that dendronized gold nanoparticles, as promising candidates for biomedical applications, can significantly affect the structural and functional properties of blood plasma proteins – human serum albumin and human alpha microglobulin;
– The mechanisms of interaction of dendrimers with proapoptotic siRNAs (siBcl2, siBCl-xL, siMcl-1) were revealed. It could be used for the development of a new approach of gene therapy of malignant cells;
– The possibility of using carbosilane and phosphorus dendrimers as carriers of antiviral ODN and siRNA directed against human immunodeficiency virus (HIV) has been studied;
– Model studies were carried out on the possibility of binding various substances by dendrimers, as a result of which the possibility of using dendrimers for binding endogenous and exogenous toxins was shown;
– The possibility of using polyamidoamine dendrimers as binding agents with an increase in the level of bilirubin in various diseases (hyperbilirubinemia, hepatitis) has been shown;
– It has been established that polylysine dendrimers have antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, as well as against fungal pathogens (Candida albicans).
– Together with BSUIR (Laboratory “Integrated Micro- and Nanosystems") and foreign colleagues (Laboratory of Coordination Chemistry CRNS, Toulouse, France), nanoparticles based on graphene, iron oxide, silver and salicylic acid, as well as amphiphilic dendrons capable of exhibiting antioxidant activity and antitumor effect in combination with drugs or miRNAs on malignant cells, have been developed.

For the laboratory’s developments, 12 inventor’s certificates and patents were received, more than 20 implementations of developments were carried out into practice and academic activity.