Institute of
bioorganic chemistry

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.

Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. That is why the development of efficient channel blockers is very important for biomedicine. At the same time, despite their pharmacological value, natural channel blockers have been previously largely neglected. Researchers from the Laboratory of Biomolecular Modeling of IBCh RAS together with colleagues from Columbia University (New York, USA) have identified structural aspects of the interaction of TRPV6 with the natural phytoestrogen genistein, which has previously shown itself in clinical studies as a blocker of cell invasion and metastasis. Using a state-of-the art biophysical approach combining cryo-EM, electrophysiology, calcium imaging, protein engineering, and molecular modeling methods, the team of scientists managed to show that genistein, binding to TRPV6, works as a pore blocker that changes the structure of the activation gate of the ion channel. The described molecular mechanism opens up new possibilities in the development of antitumor drugs. The results are published in Nature Communications. Learn more

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC₅₀ = 16 μM) close to that of Nelarabine (IC₅₀ = 3 μM) and was evaluated as active. The work is published in the International Journal of Molecular Sciences. Learn more