Institute of
bioorganic chemistry

The team of scientists from the Laboratory of Biopharmaceutical Technologies of the IBCh RAS and from the Engelhardt Institute of Molecular Biology (IMB RAS) has developed an efficient method for the preparative synthesis of modified purine 2'-deoxyribonucleosides. For this purpose, a comparative analysis of the conditions of the transglycosylation reaction catalyzed by purine (PNP) and thymidine (TP) nucleoside phosphorylases leading to the formation of 2'-deoxynucleosides, was carried out. It was shown that maximal yields of 2′-deoxyribonucleosides, especially modified, can be achieved under small excess of glycosyl-donor (7-methyl-2'-deoxyguanosine, thymidine) and a 4-fold lack of phosphate. A less than equimolar phosphate concentration allows using only a small excess of the nucleoside-donor of the carbohydrate residue to increase the yield of the reaction. The work was published in the International Journal of Molecular Sciences (IF 5.924).

A team of scientists from the Laboratory of molecular bioengineering IBCh RAS together with the colleagues from other Russian Institutes bioinformatically predicted and recombinantly produced several different depolymerases encoded in the prophage regions of Acinetobacter baumannii genomes. For two depolymerases, the specificity to capsular polysaccharides (CPSs) of A. baumannii belonging to K1 and K92 capsular types (K types) was determined. The data obtained showed that the prophage-derived depolymerases were glycosidases that cleaved the A. baumannii CPSs by the hydrolytic mechanism to yield monomers and oligomers of the K units. The recombinant proteins with established enzymatic activity significantly reduced the mortality of Galleria mellonella larvae infected with A. baumannii of K1 and K92 capsular types. These enzymes can be considered as suitable candidates for the development of new antibacterials against corresponding A. baumannii K types. The study is published in the International Journal of Molecular Sciences. Learn more

Sheath proteins comprise a part of the contractile molecular machinery present in bacteriophages with myoviral morphology, contractile injection systems, and the type VI secretion system (T6SS) found in many Gram-negative bacteria. A team of scientists from the Laboratory of molecular bioengineering IBCh RAS analysed 112 contractile phage tail sheath proteins (TShP) representing different groups of bacteriophages and archaeal viruses with myoviral morphology have been modelled with the novel machine learning software, AlphaFold 2. The common core domain of all studied sheath proteins, including viral and T6SS proteins, comprised both N-terminal and C-terminal parts, whereas the other parts consisted of one or several moderately conserved domains, presumably added during phage evolution. The results are published in the Viruses. Learn more

Understanding the relationship between genotype and phenotype, the fitness landscape, elucidates the fundamental laws of heredity and may ultimately create novel methods of protein design. In the present work a team of scientists from the Group of synthetic biology and the Group of molecular tags for optical nanoscopy IBCh RAS in the collaboration with foreign colleagues combined several approaches to engineer new variants of naturally occurring green fluorescent proteins by generating tens of thousands GFP mutant variants and assessing their ability to fluoresce. Moreover, machine learning algorithms were used for the predicting the performance of other GFP variants and expanding their fitness landscape. The published results indicate that to generate functional protein variants and to predict a protein’s function the algorithm only requires data on the effects of single-site mutations and their dependence on each other (low-order epistasis). The resulrs are published in the eLife journal. Learn more

The team of scientists from the Department of biotechnology and the Laboratory of structural biology of ion channels IBCh RAS synthesized a series of adenosine analogs as purine ribonucleosides bearing amino acid amides at the C6 position of 2-chloropurine. Molecular docking by affinity for A₁ adenosine receptors (A₁AR_s) was conducted. Colleagues from Volgograd State Medical University studied the A1AR stimulating activity in a model of an isolated mouse atrium. The investigation of A₁AR stimulating activity of synthesized nucleosides was carried out in a model of an isolated mouse atrium. Derivatives with tyrosine, valine, and serine residues exhibit the properties of A1AR partial agonists. Animal experiments in the open field test have shown that these compounds have different profiles of psychoactive action. Serine derivative has intraocular pressure-lowering effect. The synthesized nucleosides can be the basis for further design and synthesis of new A₁AR agonists. The results are published in the Bioorganic Chemistry. Learn more