Institute of
bioorganic chemistry

The antiviral T-1105 and T-705 (Favipiravir) compounds are inactive prodrugs that undergo metabolic transformation into the active form through phosphoribosylation in vivo. The efficiency of this process in human cells is very low, making the production of the phosphoribosylated pyrazine-2-carboxamide derivatives in vitro is a worthy challenge. The researchers from Dep. of Biotechnology of IBCh RAS, along with colleagues from MSU and FSRC “Crystallography and Photonics” RAS report the rational design of an efficient biocatalyst based on the hypoxanthine-guanine phosphoribosyltransferase from T. thermophilus (TthHGPRT). The rational design of TthHGPRT active site has allowed to engineer the D106G/Y155W mutant with a 325-fold increase in the rate of synthesis of T-705-riboside-5’-phosphate and 125-fold – T-1105-riboside-5’-phosphate. The reported results can become the basis for the new technologies of enzymatic production of antiviral compounds. The results are published in ACS Catalysis. Learn more

In order to assess the conservatism of the induction mechanism in different evolutionary lines of vertebrates, the Laboratory of Molecular Basis of Embryogenesis carried out studies on the functional activity of Noggin genes in the lamprey as a representative of another, evolutionarily oldest group of vertebrates – cyclostomes (jawless). It turned out that despite the conservatism of the functional properties of the studied genes in experiments with amphibians, in whose embryos the lamprey Noggins are able to induce complete secondary body axes, a similar effect was not observed in the lamprey embryos themselves. These results may indicate differences in the mechanisms of major axis induction between gnathostomes and agnathans, opening new perspectives for research into the fundamental basis of this process. The results are published in International Journal of Molecular Sciences. Learn more

The noggin1 has been described as one of the key embryonic inducers in vertebrates. Researchers from the Laboratory of Molecular Basis of Embryogenesis, Institute of Bioorganic Chemistry, Russian Academy of Sciences, have discovered a unique case of loss of the noggin1 in cartilaginous fish - ancient representatives of modern gnathostomes. The noggin2 and noggin4, conserved in sharks, were studied in the embryos of the grey catshark Chiloscyllium griseum and demonstrate similarities in expression and functional properties with orthologs in other gnathostomes. Since one of the key functions of Noggin1 is to modulate the activity of the BMP signaling pathway involved in the development of skeletal elements of the embryo, it was hypothesized that the loss of noggin1 in cartilaginous fishes is associated with the formation of their unique cartilaginous skeleton. The development of a cartilaginous skeleton and the loss of the noggin1 in cartilaginous fishes are considered to be secondary phenomena that occurred as a result of evolutionary specialization. The results are published in Scientific Reports. Learn more

This research, performed by the members of the Laboratory of Expression Systems and Plant Genome Modification (BIOTRON), Department of Plant Molecular Biology and Biotechnology, together with colleagues from the All-Russia Research Institute of Agricultural Biotechnology, reports the first time production of edited hexaploid triticale (× Triticosecale) through CRISPR/Cas9-mediated multiplexed induction of multilocular mutations in genes associated with starch biosynthesis. The results are published in Plant Cell Reports. Learn more

In response to cytomegalovirus (HCMV) infection, a pool of specialized “adaptive” NK cells with immunological memory traits develops in humans. This process is based on the recognition of HCMV peptides presented in the context of the HLA-E molecule by the activating receptor NKG2C. Using retroviral transduction, members of the Laboratory of Cell Interactions of the Immunology Department, IBCH RAS, together with colleagues from the European Medical Center, obtained K562-21E feeder cells expressing HLA-E and identified a subpopulation, whose size is associated with the magnitude of NK cell proliferative response to the presentation of the HCMV peptide. The K562-21E cells can be applied both for the accumulation of HCMV-specific NK cells and for studying the adaptive cells maturation. The results are published in Pharmaceutics.