Background. One of the perspectives of anticytokine therapy is the development of synthetic oligopeptides, which can bind and inhibit the activity of cytokines. The peptide, which is a structural analogue of the cytokine-binding region of the chemokine receptor, is of interest as a ligand for interaction with interleukin-8 (IL-8). The aim of the research was to evaluate the interaction of the Trp-Asp-Phe-Asp with IL-8. Material and methods. The interaction between the peptide and cytokine was evaluated by the change in the IL-8 concentration, which was assessed by enzyme immunoassay. Oligopeptide was used in free form adsorbed on the bottom of the plate well and immobilized in a polyacrylamide gel at a concentration of 1 µM/ml. Results. The results of the study showed that Trp-Asp-Phe-Asp, both in free and immobilized form, has the ability to bind IL-8. The maximum concentration of IL-8 bound by the free peptide is 22.13 (14.09; 30.17) pM/ml, for the adsorbed peptide – 4.22 (3.69; 4.75) pM/ml. Oligopeptide immobilized in the gel reduces the IL-8 concentration in blood plasma by 25.39 (21.34; 29.44) pM/ml. Conclusions. The results obtained are the basis for the development of medical devices for hemosorption in order to extract IL-8 from human blood plasma.

Введение. Одно из перспективных направлений антицитокиновой терапии – разработка синтетических олигопептидов, способных связывать и ингибировать активность цитокинов. Пептид, который является структурным аналогом цитокинсвязывающей области хемокинового рецептора, представляет интерес в качестве лиганда для взаимодействия с интерлейкином-8 (ИЛ-8). Цель исследования. Экспериментальная оценка взаимодействия олигопептида Trp-Asp-Phe-Asp с ИЛ-8. Материал и методы. О взаимодействии пептида с цитокином судили по изменению концентрации ИЛ-8, на основании иммуноферментного анализа. Для оценки эффективности связывания использовали свободную форму олигопептида, адсорбированную на дне лунки планшета и иммобилизованную в полиакриламидный гель в концентрации 1µМ/мл. Результаты. Анализ результатов показал, что свободная форма пептида связывает 22,13 (14,09; 30,17) пМ/мл ИЛ-8. При адсорбции пептида на дне лунки планшета его связывающая способность сохраняется, однако количество связанного ИЛ-8 снижается и составляет 4,22 (3,69; 4,75) пМ/мл. Иммобилизованный в гель олигопептид уменьшает концентрацию ИЛ-8 в плазме крови на 25,39 (21,34; 29,44) пМ/мл. Выводы. Исследования показали, что Trp-Asp-Phe-Asp как в свободной, так и в адсорбированной форме обладает способностью связывать ИЛ-8. Полученные результаты могут быть использованы в разработке изделий медицинского назначения для гемосорбции и извлечения ИЛ-8 из плазмы крови человека.

In early December 2019, the first cases of pneumonia of unknown origin were detected in Wuhan City, Hubei Province, China. High throughput sequencing has identified a novel beta coronavirus, currently called the 2019 novel coronavirus (SARS-CoV-2). Hyperinflammation in coronavirus infection (COVID-19) cause cytopenia, coagulopathy, tissue damage, liver dysfunction and macrophage activation, and also has signs of reactive hemophagocytic lymphohistiocytosis. Overproduction of inflammatory cytokines can cause organ dysfunction and ultimately death. These symptoms and associated laboratory parameters strongly resemble toxic shock syndrome, an increase in the cytotoxic adaptive immune response, when pathogenic superantigens bind to MHCII molecules and T-cell receptors (TCR). The article examines structural proteins of the coronavirus, which are involved in the development of such a response of the human immune system, discloses the molecular organization and antigenic properties of SARS-CoV-2 proteins. The role of structural molecules in the pathogenesis of coronavirus infection, as well as the possibility of their use as components of vaccines and promising ligands for efferent methods of treating this pathology, is described.

The aim of the study was the design, characteristics and analysis of the TNFα interaction with oligopeptideanalogs of the interaction site of TNFα with TNFα-R2. Here are the results of the analysis contact zone of TNFα with TNFα-R2, determination of the potentially most effective oligopeptides, study of the binding free energy of oligopeptides and its changes depending on the number of amino acid residues in the peptide chain, as well as the TNFα form (monomer or trimer). Here are described the most typical loci of oligopeptides interaction with cytokine. To confirm the calculations, the effectiveness of the selected oligopeptides was evaluated in experiments in vitro.For visualization of the molecular complex and work with the pdb file we are used Chimera 1.14 software with AutoDocVina utility. For in vitro studies, were used indirect enzyme immunoassay reagent kits. The initial concentration of oligopeptides is 10 µM, the initial concentration of TNFα (×10–8): 0; 0.0287; 0.0862; 0.2300; 0.5750; 1.4370 µM. When oligopeptides interact with mTNFα, the binding efficiency increase was observed with an increase in the number of amino acid residues in the chain. With tTNFα, such dependence was not observed. A statistically significant difference was observed in the binding energy of di-, tri-, and tetra peptides with mTNFα, with tTNFα, the differences found were not statistically significant.Thus, the data were obtained, which allowed us to come to the following conclusions: 1) the energy of interaction of oligopeptides with tTNFα does not depend on the number of amino acid residues in the oligopeptide; 2) the trimerized form of TNFα interacts most effectively with oligopeptides in comparison with mTNFα; 3) oligopeptides containing the -Trp- and being a spatial analogue of the TNFα-R2 fragment (-Trp65-Asn66-Trp67-Val68-Pro69-) interact most effectively; 4) it was selected three oligopeptides are the most promising for the binding of TNFα. The experiments in vitro confirmed the effectiveness only one oligopeptide

The S1 protein of SARS-CoV-2 (hereinafter referred to as the S1 protein) is probably the main factor in the pathogenesis of COVID-19. In our opinion, the elimination or decrease in the concentration of this protein will reduce the inflammatory process and, accordingly, damage to organs and tissues by the activated immune system. An analysis of the complexes of the Angiotensin-converting enzyme 2 (ACE2) and the S1 protein (ACE2-S1) will determine the oligopeptides that are ligands for binding the S1 protein, the timely removal of which from the blood of patients with COVID-19 will prevent the development of severe multi-organ complications. Besides, the immobilized oligopeptide that binds the S1 protein will be able to remove from the body viral particles located in the extracellular space [1].

Molecular modeling, which identified several peptide sequences, was carried out in search for compounds capable of reducing the interleukin-8 concentration in human blood plasma. The replacement of the glutamic acid residue in the Glu-His-OMe and Glu-His-Trp-OMe compounds by its cyclic form, as well as the introduction of the DTyr and DAla residues into the sequence Asp-Tyr-Ala-Pro, was shown to double their ability to bind interleukin-8.

Binding of interleukin-6 (IL-6) is the perspective target for the anti-inflammatory therapy in many pathological conditions (sepsis, autoimmune pathology, allergic diseases). The aim of this work was to develop and study the binding IL-6 oligopeptides. To achieve the goal, were set and successfully solved the following tasks: studying three-dimensional models of molecular structures of IL-6 incombination with the R-IL-6 and gp130, prediction and virtual synthesis low molecular weight oligopeptides; evaluating the free energy of IL-6 binding for identity the most effective oligopeptide; studying the changing the concentration of IL-6 inthe model solution after contact with experimental oligopeptides. In the article presents the binding IL-6 energy of 62 peptides, designed using the PyMol. Energy was calculated in the Chimera program using the AutodockVina application. There are also presented results of  in vitro  experiments interacting 7 sextapeptides, 2 tetrapeptides, and 3 tripeptides with recombinant IL-6. The effectiveness of the peptides was calculated by reducing the concentration of cytokine in solution as a percentage of the initial concentration. The free binding energy has shown that the efficiency of binding increases with an increase in the total number of amino acids and, in particular, of aromatic amino acids in the oligopeptide. Correlation analysis showed that the molecular modeling method is not absolutely effective for predicting the structure of an oligopeptide, however, it can be used as one of the preliminary steps for analyzing the interaction between molecules and studying the optimal interaction points. Two oligopeptides were identified as the most promising for further synthesis as the ligands for binding and evaluating IL-6 inhuman blood plasma.

Binding of interleukin-6 (IL-6) is the perspective target for the anti-inflammatory therapy in many pathological conditions (sepsis, autoimmune pathology, allergic diseases). The aim of this work was to develop and study the binding IL-6 oligopeptides. To achieve the goal, were set and successfully solved the following tasks: studying three-dimensional models of molecular structures of IL-6 incombination with the R-IL-6 and gp130, prediction and virtual synthesis low molecular weight oligopeptides; evaluating the free energy of IL-6 binding for identity the most effective oligopeptide; studying the changing the concentration of IL-6 inthe model solution after contact with experimental oligopeptides. In the article presents the binding IL-6 energy of 62 peptides, designed using the PyMol. Energy was calculated in the Chimera program using the AutodockVina application. There are also presented results of in vitro experiments interacting 7 sextapeptides, 2 tetrapeptides, and 3 tripeptides with recombinant IL-6. The effectiveness of the peptides was calculated by reducing the concentration of cytokine in solution as a percentage of the initial concentration.The free binding energy has shown that the efficiency of binding increases with an increase in the total number of amino acids and, in particular, of aromatic amino acids in the oligopeptide. Correlation analysis showed that the molecular modeling method is not absolutely effective for predicting the structure of an oligopeptide, however, it can be used as one of the preliminary steps for analyzing the interaction between molecules and studying the optimal interaction points. Two oligopeptides were identified as the most promising for further synthesis as the ligands for binding and evaluating IL-6 inhuman blood plasma.