Institute of
bioorganic chemistry

The luciferin of the bioluminescent system of O. undecimdonta, which emits green-blue light, is an unusual heterocycle with previously unknown thieno[3,2-f]thiochromene skeleton. Despite numerous methods for the synthesis of benzothiophenes and thiochromenes, no synthetic approaches to thieno[3,2-f]thiochromenes have been proposed so far. The researchers from the Laboratory of Chemistry of Metabolic Pathways developed a convergent synthetic pathway to thieno[3,2-f]thiochromene tricarboxylate via cascade reactions with the use of bifunctional reagents, which afforded the structural confirmation of Odontosyllis undecimdonta luciferin and opened the route to other thieno[3,2-f]thiochromenes that were not accessible via known synthetic methods. The research was published in Organic Letters. Learn more

Scientists from the Department of Molecular Neuroimmune Signaling IBCh RAS together with colleagues from the Institute of Cell Biophysics and the Institute of Theoretical and Experimental Biophysics, studied the effect of cobra venom cardiotoxins on the intracellular concentration of calcium ions and the shape of rat cardiomyocytes (CaTx). Depending on the structure of the N-terminal or the central polypeptide loop, CaTx are classified into either group I and II or P- and S-types, respectively. It was shown that CaTxs of group I containing two adjacent proline residues in the N-terminal loop were less toxic to cardiomyocytes than group II toxins and CaTxs of S-type were less active than P-type ones. So, it was demonstrated that the CaTx toxicity to cardiomyocytes depends on the structures both of the N- terminal and central polypeptide loops. The paper was published in the International Journal of Molecular Sciences. Learn more

Scientists from the IBCh RAS together with the EIMB RAS and Sirius University, carried out a comparative analysis of the fractions of circulating CD56⁺ NKT-like cells, combining the properties of T- and NK-cells, and CD56^– T-lymphocytes in COVID-19 among patients in intensive care units (ICU), patients with moderate severity and convalescents. ICU patients with a fatal outcome had a reduced percentage of NKT-like cells, which indicates the potential role of this cell fraction in the pathogenesis of COVID-19. Scientists propose to consider a decrease in the proportion of NKG2D⁺ and NKG2A⁺ cells and an increase in the expression of PD-1 and HLA-DR in both CD56^– and CD56⁺ T cells as markers of COVID-19 progression. The results are published in the International Journal of Molecular Sciences.

Two forms were found in the NMR spectra of N⁶-substituted 2-chloroadenosines. The proportion of the mini-form was 11–32% of the main form. It was characterized by a separate set of signals in NMR spectra. The team of scientists from IBCh RAS assumed that the mini-form arises due to an intramolecular hydrogen bond between the N⁶–CH proton of the substituent and the N7 atom of purine. The ¹⁵N-HMBC spectrum confirmed the presence of a hydrogen bond in the mini-form of the nucleoside and its absence in the main form. Compounds incapable of forming such a hydrogen bond were synthesized. In these compounds, either the N7 atom of the purine or the N⁶–CH proton of the substituent was absent. The mini-form was not found in the NMR spectra of these nucleosides, confirming the importance of the intramolecular hydrogen bond in its formation. The results are published in the International Journal of Molecular Sciences.

In a joint review with Italian colleagues, the prospects for the use of metal-based nanoparticles (MNPs) to overcome the low response to cancer immunotherapy were considered. Such nanoparticles are inherently exogenous agents and are able to activate the immune response through pattern recognition receptors. When administered locally (intratumorally), MNPs can act as adjuvants, enhancing the action of immunomodulators, including immune checkpoints. This can enhance the immune response and spread it to distant tumors and metastases (manifestation of the abscopal effect). The most recent works and approaches able to enhance immunotherapy are discussed. Particular attention is paid to the cancer-immunity cycle and the role of innate immunity cells. The general prerequisites for the development of effective combined anticancer drugs based on MNP and immunomodulators are suggested. The review is published in Pharmaceutics.