Russian Journal of Bioorganic Chemistry
The Journal was founded in 1975 by Prof. Yurii A. Ovchinnikov. The Editorial Board uses the term "bioorganic chemistry" to cover a wide range of problems related to the investigation of the structure and function of biomolecules using the methods of organic, biochemical and physical chemistry.
The journal is intended for scientists, for those in the health professions, educators, and students in universities and researchers in industrial, medical, agricultural, and environmental control laboratories.
Russian Journal of Bioorganic Chemistry (Bioorganicheskaya Khimiya) welcomes papers on all aspects of bioorganic chemistry, biochemistry, cell and molecular biology, genomics, proteomics, bioinformatics, immunology, molecular virology, molecular evolution and developmental biology.
The Journal publishes reviews, minireviews, research articles and theoretical investigations, hypothesis and short communications.
The Journal is published in Russian (under the name Bioorganicheskaya Khimiya in the Russian Federation) and in English (under the name Russian Journal
of Bioorganic Chemistry) six times a year by Russian Academy of Sciences (IKC "Akademkniga") in Moscow (Russia) and Pleiades Publishing Inc. in the United States. The English edition is distributed worldwide by Springer.
Articles are published in Russian and English. Publication of articles in the Russian Journal of Bioorganic Chemistry (Bioorganicheskaya Khimiya) – free.
Media registration certificate: № 0110214 от 08.02.1993
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Vol 51, No 6 (2025)
ОБЗОРНЫЕ СТАТЬИ
Clinically Significant Panallergens in Development Sensitization and Methods of Their Diagnosis
Abstract
Among related proteins of plant or animal origin, which are widespread in nature, there are families capable of causing cross-IgE-mediated reactions in the body. Such families of proteins are called panallergens. Each family of these proteins has its own physico-chemical and immunobiological features, which affects their allergenic properties. This review describes the main families of panallergens, their structure, properties, functions and possible consequences of sensitization of patients, as well as modern methods of molecular allergodiagnostics. The review provides a summary table on the protein families of pan-allergens. The choice of the treatment method for patients with allergopathology, the selection of elimination measures, and especially allergen-specific immunotherapy largely depend on the accurate and early diagnosis of allergic diseases. As with any pathology, therapy is effective in allergic diseases only when it is pathogenetically justified, when an integrated approach is applied and the sequence of therapeutic measures is followed. Accordingly, knowledge of the families of panallergens and their properties makes it possible to more competently identify cross-reactions in patients with allergopathology and specifically select the necessary treatment for them.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1011-1026
1011-1026
ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ
Assessment of Adaptive Immune Response Against Influenza Using Synthetic Peptides
Abstract
This study tested a method for assessing the immunogenicity of synthetic peptides, which could form the basis for a clinical diagnostic method for the cellular immune response to influenza A virus. The two peptides used are identical in amino acid composition to the 9-mer epitopes of influenza virus surface proteins relevant to the vaccine strains of the Northern Hemisphere for the 2023–2024 season and represent a fragment (432–440 aa) of influenza A virus hemagglutinin (Phe-Leu-Asp-Ile-Trp-Thr-Tyr-Asn-Ala) and a fragment (454–462 aa) of influenza B virus neuraminidase (Leu-Leu-Trp-Asp-Thr-Val-Thr-Gly-Val). The peptides were synthesized using classical methods of peptide chemistry, with activated esters and the carbodiimide method as the main condensation methods. Fifty-five volunteers aged 20–26 years participated in the clinical study. Gamma interferon (IFN-γ) levels were assessed by enzyme-linked immunosorbent assay. No statistically significant results were obtained for all pairwise comparisons of IFN-γ concentrations in 55 cases. This method needs to be optimized for clinical diagnosis of the cellular immune response to influenza A virus.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1027-1037
1027-1037
Mono- and Dihydrazones with a 6-Methyluracil Fragment: Synthesis, Cytotoxicity, and Antioxidant Activity
Abstract
6-Methyluracil is an important compound that plays an active role in cell regeneration processes. Its ability to stimulate cell growth and replication is a key factor in the tissue healing process. Methyluracil accelerates the skin repair process, which makes its use indispensable in dermatology and surgery for the treatment of wounds, ulcers and burns. Carboxylic acid hydrazides are also of interest due to their unique coordination-chemical properties and are used in various industries. In medicine, hydrazides exhibit a wide range of activity: they have anti-tuberculosis, antiviral and antibacterial effects. Some heterocyclic hydrazones have been show to be inhibitors of the main protease of SARS-CoV-2. This highlights the importance of studying the structural and functional features of these compounds. The synthesis of hydrazones with a 6-methyluracil fragment is a promising area in the field of pharmaceutical chemistry and medicine, opening up new opportunities for the development of innovative drugs. In this work, dihydrazones were synthesized based on dihydrazides of carboxylic acids (adipic, azelate, and sebacic) with fragments of 6-methyluracil. Using the online version of the OCHEM expert system, an in silico assessment of the spectrum of biological activity was performed, including cytotoxicity, antioxidant activity, acute toxicity and hematotoxicity of the obtained compounds and comparison drugs. Studies of biological activity have shown that the obtained mono- and dihydrazones do not have cytotoxic effects on the studied tumor cell lines (HepG2, AS49, MCF-7, HCT-116) and the conditionally normal HEK 293 cell line. Moderate selective cytotoxicity of 6-methyl-5-[(2-phenylhydrazono)methyl]pyrimidine-2,4(1H,3H)-dione has been established in relation to human colorectal carcinoma (HCT-116 cell line, IC50 = 71.75 ± 8.29) and the conditionally normal HEK 293 cell line (IC50 = 19.35 ± 2.12). The antioxidant activity of mono- and dihydrazones was studied using methods of reduction of Fe3+ cation radical ABTS and stable radical DPPH in vitro. A leader compound has been identified (3-(2-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)methylene)hydrazinyl)-benzoic acid), comparable in antioxidant activity to ascorbic acid, for in-depth study.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1038-1050
1038-1050
Features of Synthesis and Study of Toxic Properties of Tryptophan-Containing Analogue of Arginine-Vasopressin
Abstract
Among the previously studied analogues of the C-terminal fragment of arginine vasopressin (AVP), the tetrapeptide Ac-Trp-Pro-Arg-Gly-NH2 is of great interest as a potential pharmaceutical substance. It demonstrated antidepressant-like and anxiolytic activity at doses of 0.10–10 μg/kg in experiments with rodents. In this paper, we consider the features of the synthesis of a tryptophan-containing analogue of AVP, and propose a new "block" scheme for obtaining the peptide, which allows it to be produced in higher yields than shown previously. Experiments were conducted to study the toxic properties of Ac-Trp-Pro-Arg-Gly-NH2. Under these conditions, the peptide did not exhibit any clearly expressed pathological effect on the internal organs of experimental mice, and also showed no cytotoxicity in the range of expected therapeutic doses (IC50 >1000 μM). The low toxic effects of tryptophan-containing AVP analogue demonstrated in this work makes the tetrapeptide a promising substance for further studies of biological activity, toxicity and mechanisms of action with the aim of creating new, safer and more effective anxiolytics and antidepressants based on it.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1051-1062
1051-1062
Spatial Structure of the C-Terminal Domain of Bacillus cereus Hemolysin II is Stabilized in the Composition of the Full-Size Toxin
Abstract
Hemolysin II (HlyII) is one of the key pathogenic factors of Bacillus cereus, a pore-forming toxin with a spatial structure of the β-barrel type, possessing a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD). In this work, site-directed mutagenesis of amino acid residues lying on the surface of the HlyIICTD protein globule was carried out. The work has been demonstrated that the C-terminal domain can simultaneously exist in several structural isoforms. The move of the three-dimensional structure of HlyIICTD into a stable form as a part of water-soluble full-length toxin monomer is observed. Recombinant proteins and their mutant forms using producing strain Escherichia coli BL21 (DE3) were obtained. Their interaction with monoclonal antibodies HlyIIC-16 and HlyIIC-23 by enzyme immunoassay was studied. To define the epitopes of the phage display of HlyIIC-16 and HlyIIC-23, site-directed mutagenesis, gene cloning of individual parts of the HlyIICTD molecule, three-dimensional modeling of HlyIICTD fused to SlyD using the AlphaFold program were used. It was shown that monoclonal antibodies obtained against HlyIICTD interacted with intact HlyIICTD much more effectively than with the full-length toxin and the chimeric protein – HlyIICTD fused with SlyD. Antibodies HlyIIC-16 and HlyIIC-23 effectively inhibited each other's interaction with immobilized HlyIICTD in an enzyme-linked immunosorbent assay, indicating the proximity of their epitopes on the surface of the HlyIICTD molecule. Phage display, site-directed mutagenesis, and gene cloning of individual parts of the HlyIICTD molecule were used to determine the epitopes of HlyIIC-16 and HlyIIC-23. Spatial modeling of HlyIICTD fused to SlyD using the AlphaFold program suggested the location of the HlyIIC-16 and HlyIIC-23 epitopes on the Gly341–Gly364 region of the HlyII protein. It was demonstrated that the C-terminal domain can simultaneously exist in several structural states (isoforms). In the water-soluble form of the full-length toxin monomer, a transition of the spatial structure of HlyIICTD to a stable form is observed.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1063-1074
1063-1074
New Conjugates of 3'-Azido-3'-deoxythymidine and 2',3'-Dideoxy-3'-thiacytidine Based on 1,3-(Dipalmitoylamino)-propan-2-ol: Synthesis and Investigation of Anti-Hiv Activity on Model Cellular Systems
Abstract
The development of prodrugs of antiviral nucleosides with isosteric derivatives of natural lipids makes it possible to increase the bioavailability of these drugs and modulate their effectiveness. In this work, new lipophilic prodrugs of 3'-azido-3'-deoxythymidine (AZT), 2', 3'-dideoxy-3'-thiacytidine (3TC) based on 1,3-(dipalmitoylamino)propane-2-ol were synthesized by using the H-phosphonate method, as well as phosphoramidate derivatives modified by the phosphorus center with various esters of L-α-alanine. The anti-HIV activity of the synthesized compounds against various HIV strains (HIV-1 MVP-899, HIV-1 RF) and cytotoxicity against MT-4 cells have been studied. H-phosphonate ester and phosphodiester conjugates showed lower anti-HIV activity than the original nucleosides (EC50 = 0.59–3.04 μM), their advantages include low cytotoxicity (CC50 > 100 μM), while the phosphodiester conjugate 3TC was inactive on this cellular model of the virus. The antiviral activity of phosphoramidate derivatives with L-α-alanine esters decreased in the range (tBu) > Me > (iPr) > Et, EC50 values were 0.46, 4.60, 8.97, and 12.55 μM, respectively, and these compounds exhibited cytotoxicity similar to AZT (CC50 > 50 μM). An additional advantage of such conjugates may be the possibility of targeted transport into HIV reservoirs due to enterocyte-mediated lymphatic transport, as well as the potential intracellular release of nucleoside monophosphate, which makes it possible to bypass the limiting stage of phosphorylation of nucleosides to their active triphosphate form. Therefore, the development of such prodrugs can serve as a basis for the search for drugs with high efficacy.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1075-1087
1075-1087
Three-Dimensional Structure of the Orange-Red Fluorescent Biomarker DiB3-F53L
Abstract
The 3D structure of the fluorescent protein DiB3-F53L, an orange-red fluorescent non-covalent complex of a genetically engineered variant of the bacterial protein lipocalin Blc with a synthetic GFP-like chromophore M739, was studied by the molecular dynamics (MD) computational method. The chromophore was shown to interact more strongly with the mutated DiB3-F53L protein than with the native DiB3 protein. Calculations revealed the amino acids surrounding the chromophore at the binding site that contribute most strongly to the chromophore-protein interaction energy. The DiB3-F53L protein complex with the M739 chromophore exhibits increased fluorescence brightness compared to the known parent biomarker DiB3, making it a promising marker for labeling biological objects in cell biology, as well as a starting point for the subsequent design of new, brighter biological markers.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1088-1092
1088-1092
Determination of IgG and IgA Antibodies by Fluorescence Polarization Using Fluorescently Labeled Recombinant Nanobodies
Abstract
Quantitative, rapid and high-throughput analysis of IgG and IgA immunoglobulins is necessary to determine the content of these proteins and their associated molecules in the patient's physiological fluids. The analysis of these proteins is necessary in the diagnosis of specific antibody deficiency as an auxiliary test for the detection of general variable immunodeficiency, as well as for risk stratification of patients with low IgA levels. IgG content determination can help in prescribing revaccination to patients and supporting their treatment strategy, can be used to monitor the patient's humoral immune system, as well as in the development and subsequent production of most therapeutic antibodies in biopharmaceuticals. Miniature recombinant single-domain antibodies (nanobodies) have a number of advantages over classical antibodies, such as their relative simplicity of operation, high stability over a wide range of temperature and pH values, the ability to recognize highly specific conformational epitopes of the target protein, as well as the possibility of using them as probes for detecting larger target antigen proteins in the fluorescence polarization method. Fluorescently labeled FITC-anti-IgG and FITC-anti-IgA nanobodies to human IgG and IgA were obtained and characterized. The Kd values of the FITC-anti-IgG*IgG and FITC-anti-IgA*IgA complexes were determined, they confirmed the high affinity of the immunoreagents. The possibility of specifically determining IgG and IgA levels in human serum in the range of 35–120 µg/mL (for IgA) and 75–260 µg/mL (for IgG) was demonstrated. Eighteen human sera were tested for IgG and IgA levels, and the content of antibodies in the samples was confirmed using commercial enzyme immunoassay kits. FITC-anti-IgG and FITC-anti-IgA did not interact with other human proteins: albumin, plasminogen, fibrinogen, lactoferrin, and transferrin. Testing of human and animal sera by FITC-anti-IgG and FITC-anti-IgA demonstrated specific binding to human and monkey antisera, but not to animal sera: bovine, canine, feline, rabbit, and sheep. Thus, the FPIA method can be used for the rapid and specific determination of human IgG and IgA.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1093-1105
1093-1105
Synthesis and Biological Properties of Pyridoxine Derivatives Containing 1,3-Oxazolidine-2-one Fragments
Abstract
A library of 11 pyridoxine derivatives with 1,3-oxazolidin-2-one fragments in positions 2, 5, and 6 was synthesized. Studies of the antibacterial activity of the obtained compounds on 6 reference and 6 clinical strains of Gram-positive bacteria and cytotoxicity against conditionally normal human cells in vitro revealed a highly active and low-toxicity lead compound containing a 1,3-oxazolidin-2-one fragment in position 5 of pyridoxine. Further in-depth studies of this compound against bacterial biofilms of S. aureus and E. faccium demonstrated comparable and, in some cases, superior efficacy to the drug linezolid. At the same time, unlike linezolid, the lead compound does not exhibit a mutagenic effect in the Ames test and is highly safe when administered intragastrically to mice (LD50 >2000 mg/kg).
Russian Journal of Bioorganic Chemistry. 2025;51(6):1106-1132
1106-1132
Synthesis and Antibacterial Activity of Ethynyl and Azido Derivatives of N4-Dodecylamino-2'-deoxycytidine
Abstract
Methods for obtaining new derivatives of N4-dodecylamino-2'-deoxycytidine and cytidine have been developed. The new derivatives contain 5-ethynyl, 5-(prop-2-in-1-yl)oxymethyl or 5'-azido groups necessary for the introduction of dyes in vitro using click chemistry methods. The obtained compounds, as well as N4-dodecylamino-2'-deoxycytidine, showed significant antibacterial activity against Gram-positive bacteria. The new nucleosides can be used to visualize their subcellular localization in order to determine the possible mechanism of action of antibacterial agents of this kind.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1133-1141
1133-1141
N4-(ω-Aminoalkyl)- and N4-(ω-Dansylaminoalkyl)-5-methyl-2'-deoxycytidines
Abstract
New derivatives of N4-(dodecyl)-5-methyl-2'-deoxycytidine containing terminal amino groups at the end of an alkyl linker have been synthesized. It is shown that they are convenient syntones for the subsequent introduction of dansyl fluorophore groups. One of the N4-ω-dansylaminoalkyl derivatives has showed moderate antibacterial activity against the Mycobacterium smegmatis strain. This derivative can be used to study the subcellular localization of this kind of compounds.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1142-1147
1142-1147
Composite Aerogel Materials with Hemostatic Effect Based on Alginate and Chitosan
Abstract
Currently, there is a high global demand for new, effective hemostatic materials. Highly porous organic aerogels derived from bioactive polysaccharides of marine origin, such as sodium alginate and chitosan, show great promise for these applications. Due to their advanced structure and natural origin, these materials possess important properties such as biocompatibility, biodegradability, nontoxicity, chemical inertness, fibrousness, mechanical strength, and water insolubility. In this study, composite aerogel materials were synthesized from a combination of alginate and chitosan, with the addition of active additives (magnetite and vaterite). Their properties were evaluated to assess their potential as hemostatic materials. The results show that the developed materials feature a well-developed micro-mesoporous structure, which provides a high moisture absorption capacity when exposed to a saline solution, simulating the pH of warm-blooded animals. The maximum absorbency was 67 and 43 g/g for the materials containing vaterite and magnetite, respectively, which can be attributed to differences in their porous structures. The antimicrobial activity tests confirmed the suitability of these materials for biomedical applications. The materials exhibited the strongest antibacterial activity against Staphylococcus aureus and Bacillus subtilis, with growth inhibition zones of 24 ± 0.2 and 20 ± 0.2 mm, respectively. A comparative analysis of their hemostatic performance in vivo demonstrated that the materials are capable of stopping bleeding at a higher rate than a cotton swab. Specifically, the blood clotting times for the materials containing vaterite and magnetite were 32.64 and 49.61 s, respectively, which is 1.3 to 2 times faster than the control group. These findings indicate that composite aerogel materials based on a complex of sodium alginate and chitosan, with the inclusion of active additives (magnetite and vaterite), have strong potential to compete in both the international and Russian markets for hemostatic drugs and medical devices.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1148-1158
1148-1158
Assessment of Toxicity, Genotoxicity, and Cytotoxicity of Phenycycloalkanpolycarboxylic Acids: A Study with Allium cepa and Chlorella vulgaris
Abstract
To assess the toxicity, cytotoxicity, and genotoxicity of polycarbonic acids containing cycloaliphatic fragments, a comprehensive approach was used, based on the application of test organisms (the unicellular green alga Chlorella vulgaris and onion Allium cepa). The polycarbonic acid compounds were evaluated at concentrations of 1.0, 0.1, 0.001, and 0.0001%. It was shown that the polyacids were not mutagenic in the Allium cepa based bioassay, but high concentrations of the compounds could lead to an increase in the mutation frequency of Chlorella vulgaris. These results justify the need for further research to comprehensively evaluate the safety and potential applicability of these compounds. The approach described here can be applied to obtain quick, cost-effective, and useful supplementary data on various types of toxicity in vitro for substances with potential biological activity.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1159-1166
1159-1166
Analysis of the Protein-Protein Interaction of CREBBP, HTT, and KMT2D by Principal Components Method
Abstract
The transcriptional coactivator CREBBP (cyclic AMP response element binding protein-binding protein), neuron-specific transcriptional regulator HTT (huntingtin) and histone-lysine methyltransferase KMT2D (lysine methyltransferase 2D) cooperatively participate in post-translational modification of histones and regulation of differential gene expression. The mechanism of protein-protein interactions has been poorly studied. Computer analysis of the primary structure of proteins using the principal components method revealed the presence of the highest possible correlation between the main components of amino acid sequences in the CREBBP–HTT and CREBBP–KMT2D pairs with glutamine. The trajectory of the first principal component of CREBBP practically coincides with the graph of the positional frequency of glutamine along the protein molecule. It is shown that in the secondary structure of CREBBP a significant share is occupied by E-strand (extended strand) elements with an open conformation of the peptide chain. Polyglutamine tracts localized at the C-terminus of CREBBP, N′-terminus of HTT, N-, C-termini and in the center of KMT2D also have an open conformation facilitating the formation of intermolecular hydrogen bonds. It is assumed that the polyglutamine tracts of the C-terminus of CREBBP and the N-terminus of HTT are directly involved in the protein-protein contact of CREBBP–HTT. A similar connection between the polyglutamine tracts of the C-terminus of CREBBP and the central region of KMT2D fixes the physical interaction in this pair of proteins. The identified features of the studied proteins can be used to design new pharmacological drugs using physicochemical methods.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1167-1174
1167-1174
ПИСЬМА РЕДАКТОРУ
Kaede Protein Chromophore Analogue as a Tool for Simultaneous Selective Staining of the Nucleus and Mitochondria
Abstract
A series of three dyes – analogs of the chromophore of the fluorescent protein Kaede with various substituents – was synthesized. Based on fluorescence microscopy results, a promising fluorogen was identified: 5-((Z)-2-(difluoroboranyl)-4-(dimethylamino)-5-hydroxybenzylidene)-3-methyl-2-((E)-2-(pyridin-4-yl)-vinyl)-3,5-dihydro-4H-imidazol-4-one. The successful application of this dye in wide-field fluorescence microscopy for simultaneous selective staining of nuclei and mitochondria in living cells was demonstrated using the HeLa Kyoto cell line as an example. The synthesized compound may find application in the field of visualization of living system processes.
Russian Journal of Bioorganic Chemistry. 2025;51(6):1175-1180
1175-1180