Том 45, № 2 (2019)

One of the means for regulating the plant innate immune system is activating the synthesis of various defense peptides having diverse structural organization. Some of them possess antimicrobial activity. In plants, defense peptides have various localization; they are often synthesized as multidomain precursor proteins or produced by limited proteolysis, as well as through other degradation pathways. In addition to antimicrobial activity, some of these peptides also display an insecticidal effect, inhibit endo- and exogenous proteases, as well as α-amylases, participate in the transfer of building and signaling hydrophobic molecules, and affect the functioning of ion channels. As a result, peptides of plant innate immune systems not only protect plants against viruses, bacteria, fungi, and insects, but also reinforce their resistance to various types of abiotic stresses and participate in the regulation of plant growth and development. In addition, plant defense peptides can suppress the growth of some human pathogens, possess antitumor activity, exhibit properties of food, inhalation, and latex allergens, and can be used in various areas of medicine. This review summarizes data on biosynthesis, biological functions, and possible practical application of the peptides of the plant innate immune system.

The review is devoted to promising directions of the search for chemical compounds which can be used as the basis for the development of new drugs for migraine treatment. It considers promising biological targets, whose effects are capable of eliminating the manifestations of acute migraine attacks, and also indicates the main existing developments in the form of chemical compounds and drug prototypes interacting with these targets, including those that will soon enter or are at the stage of clinical trials. In particular, preclinical and clinical data on compounds whose effects are determined by the influence on the calcitonin gene-related peptide (CGRP) receptors, serotonin 5-HT_2A and 5-HT_1F receptors, NO-synthase, orexin and glutamate receptors, are discussed. The review focuses on the description of 5-HT_2A receptors as a promising target for the development of novel antimigraine drugs. Information about the structural features of this serotonin receptor subtype, the localization and functions is given; also it involves the pharmacological capabilities of new substances affecting 5-HT_2A receptors. The final part of the review is devoted to new trends in the search for 5-HT_2A antagonists among compounds synthesized based on a serotonin bioisostere, benzimidazole.

Polypeptide SE-33 (SETRPVLNRLFDKIRQVIRKFEKGIKEKSKRFF), which is a retro analog of natural antimicrobial protein cathelicidin LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), was synthesized by the method of solid-phase peptide synthesis. Similar to the natural peptide, polypeptide SE-33 forms an amphipathic alpha helix but has an inverted amino acid sequence compared to cathelicidin. It has been shown the physicochemical properties of polypeptide SE-33 are similar to those of the natural compound. In vitro experiments have shown that polypeptide SE-33 exerts a bactericidal effect on the cells of Staphylococcus aureus Wood 46, which is comparable with the effect of cathelicidin LL-37, as well as pronounced antifungal activity against the clinical isolates of Candida albicans, Cryptococcus neoformans, Rhodotorula mucilaginosa, Trichosporon cutaneum, Geotrichum sp. The MICs of polypeptide SE-33 for different fungal strains were in the range of 31.2 to 1024 μg/mL. Polypeptide SE-33 demonstrated high activity in vivo in the model of vulvovaginal candidiasis (VVC) in mice comparable with that of pimafucin. In the absence of side effects and signs of pathology, polypeptide SE-33 in all doses tested (1, 10 and 50 mg/mL) statistically reduced the vaginal load of the mice compared to the placebo group. The pronounced antibacterial and antifungal activity of polypeptide SE-33, as well as the absence of a toxic effect in the VVC model in mice, suggest polypeptide SE-33 as a promising antimicrobial agent.

A proteomic analysis of the venom of males and females of the Naja kaouthia monocled cobra specimens kept in captivity was carried out. Using the amino acid sequences of proteins of the taxonomic group Serpentes from the UniProt KB database, 875 proteins were identified in the venom samples and the relative content of about 190 of them was determined in each venom sample by the method of label-free quantitative proteomics. The total content of 35 major protein components of the venom of each individual was shown to comprise about 98% of the total amount of venom proteins. Analysis of relative content of the venom proteins in males and females showed a significantly (p < 0.05) higher content of nerve growth factor and natriuretic peptide in the venom of females. Analysis of the profile of posttranslational modifications of N. kaouthia toxins revealed previously unknown sites for phosphorylation, acetylation, and formylation.

A radioligand-based method was proposed for quantifying the binding activity of β1-adrenergic receptors (ARs) on the surface of human T lymphocytes. Using the transfected HEK293 cell lines expressing β1-AR (ADL-7A) and β2-AR (A2R9) as a model, the conditions for [¹²⁵I]cyanopindolol reliable detection of specific ligand binding to β1-adrenergic receptors at the level of 1–1.5 fmol per 1 million cells were selected. The real possibility of performing this analysis for clinical studies was shown by the example of human T lymphocytes.

Diketone DNA derivatives have been proposed to modify the guanidine group of Arg in proteins. The β-diketo group at the C2' atom of the sugar phosphate moiety has been introduced in DNA by acylation of oligonucleotide precursors, i.e., DNA fragments containing 2'-amino-2'-deoxyuridine, which have been synthesized by the chemical automatic synthesis. Water-soluble N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide (EDC) and 4,6-dioxoheptanoic acid have been used in the reaction. The ability of oligodeoxyribonucleotides containing the 2'-β-diketo group to react with guanidine, N^α-Boc-L-arginine, and N^α-Dns-L-arginine has been demonstrated. The introduction of this modification into one of the strands of the 15-base pair DNA duplex has been shown to lead to its destabilization. The conjugate formation of MutS and MutL proteins from the E. coli mismatch repair system with 17-base pair DNA duplexes containing the 2'-deoxy-2'-(4,6-dioxoheptylamido)uridine residue has been detected for the first time. To increase the selectivity of the DNA ligands containing the β-diketo group in the reaction with the Arg residues of proteins, we have proposed to treat the reaction mixture with hydroxylamine. This treatment leads to the cleavage of Schiff bases, which are formed with the involvement of lysine residues.

The early period of postnatal development of premature infants is often complicated by bacterial infections, in particular respiratory infections, which in adverse course can be transformed into generalized forms (sepsis), leading to life-threatening conditions. The development of these complications may be associated with delayed diagnosis and delayed start of targeted therapy. Thus, the development of new approaches to the diagnosis of inflammatory pathological processes, especially in the first hours of life, is an important area of research in modern neonatology. In this work the profiling of blood plasma lipids from newborn premature babies was performed in order to identify potential markers of inflammatory processes. The study involved three groups of patients who were diagnosed with pneumonia, pneumonia complicated by sepsis, or respiratory distress syndrome in the early postnatal period. As a result of HPLC-MS analysis of blood plasma lipid extracts, characteristic molecular profiles were obtained, which revealed significant differences between the groups under study. Analysis of the molecular composition showed differential representation of lipid classes such as phosphatidylcholines, phosphatidylethanolamines, di- and triglycerides, sphingolipids and lysophospholipids. Our results may indicate that the inflammatory processes at the local and systemic levels affect lipid metabolism and their composition in blood plasma. Moreover, each pathology—sepsis, pneumonia or RDS—has its own specific lipid profile, which may be useful not only to detect inflammation but also to differentiate inflammation-associated diseases from each other.

The insulin receptor-related receptor (IRR) is a cellular sensor of a weakly alkaline medium. Its spatial structure and the mechanism of activation have not been yet established. In the present work, a system of heterologous expression of full-length IRR tyrosine kinase has been created. A plasmid construct encoding the cDNA of the full-length human IRR fused at the C-terminus with the green fluorescent protein (GFP) has been generated, and the hybrid protein has been expressed in HEK293 line cells. It has been shown that the receptor incorporated in the hybrid protein is expressed on the cytoplasmic membrane and retains its functional activity. The resulting protein can be used in further studies of the structure and function of IRR.