Institute of
bioorganic chemistry

A duplication of the chromosomal region 2q23.q23.2, carrying LYPD6 and LYPD6B genes, leads to intellectual disability and autistic features. Researchers from the Neurotransmitter and Neuroreceptor Bioengineering Laboratory, Shemyakin-Ovchnnikov Institute of Bioorganic Chemistry of RAS together with colleagues from Lomonosov State University and Institute for Biomedical Problems of RAS, used a mouse model to study the consequences of overexpression of the Lypd6 and Lypd6b proteins in the brain, which is typical for patients with autism and other neuropsychiatric disorders. A two-week intracerebral infusion of recombinant Lypd6 and Lypd6b analogs impaired memory, increased acute anxiety, reduced dendritic spine density in the hippocampus and amygdala, and led to decreased expression of endogenous Lypd6, Lypd6b, and the α7 nicotinic receptor in the hippocampus. Moreover, in the work I shown that Lypd6b, Like Lypd6, is a negative allosteric modulator of nicotinic receptors. The work is supported by the Russian Science Foundation and published in the journal Cell Death Discovery (IF 6.1).

Phage φ29 and related bacteriophages are currently the smallest known tailed viruses infecting various representatives of both Gram-positive and Gram-negative bacteria. Searches conducted using public genomic databases revealed in excess of 2000 sequences that share the characteristic features of phage φ29. An analysis of major capsid proteins (MCPs) of φ29-related phages indicated the dissimilarity of MCP sequences to those of almost all other known Caudoviricetes groups and a possible distant relationship to MCPs of T7-like phages. Sequence searches conducted using HMM revealed the relatedness between φ29-like phages and an unusual lactococcal phage, KSY1 (Chopinvirus KSY1), whose genome contains two genes of RNA polymerase. The combination of the unique features and distinctive origin of φ29-related phages suggests the categorisation of this vast group in a new order or as a new taxon of a higher rank. The results are published in the International Journal of Molecular Sciences. Learn more

Identifying high-affinity antibodies in human blood serum is a non-trivial task due to the extremely small number of circulating B-cells with the specified specificity. A team of scientists from the IBCh RAS proposed an effective approach that allows for the identification of high-affinity antibodies against pathogen proteins while simultaneously mapping epitopes, even in the absence of information about the structure of the pathogen's immunogens. To screen therapeutic antibodies in the blood of recovered donors, only the pathogen's transcriptome is needed to create a polypeptide library of antigens displayed on the surface of a bacteriophage. The work was published in the journal Communications Biology. Learn more

Scientists from the departments of biotechnology and structural biology (IBCH RAS) and Institute of the Chemistry of Plant Substances (Uzbekistan), and D. I. Ivanovsky Institute of Virology synthesized a series of substituted 1,2,4-triazole-3-thione nucleoside analogs and tested their antiviral activity against herpes simplex virus. 1,2,4-Triazole derivatives have a wide range of biological activities and finding new nucleosides based on it is a topical task. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. For ribosides and deoxyribosides produced by enzymatic synthesis, it has been shown that the addition of carbohydrates to mono- and di-substituted 1,2,4-triazole-3-thiols occurs at different nitrogen atoms. All synthesised nucleosides and heterocyclic bases were tested for cytotoxicity and activity against herpes simplex virus 1. Compared to the antiviral drug ribavirin, the selectivity index for the two nucleosides was significantly higher. It was also found that as the lipophilicity of the compounds studied increased, both their activity and toxicity increased. The results are published in the Biomolecules (IF 4.8). Learn more

The papain-like protease PLpro plays a key role in the life cycle of the coronavirus SARS-CoV-2, making this enzyme a promising target for antiviral therapy. In this work a genetically encoded fluorescent sensor for PLpro activity was created. A distinctive feature of the sensor is its design closely mimicking the natural target of PLpro. A high-contrast translocation response (14-fold change in the signal ratio in the nucleus and cytoplasm) makes it possible to reliably detect PLpro activity in human cell cultures not only in the recombinant protease overexpression model, but also during infection with the SARS-CoV-2 virus, as a team of scientists from the Laboratory of genetically encoded molecular tools of IBCH RAS has shown in collaboration with Institute of Molecular Biology of the Russian Academy of Sciences and the Gamaleya Center for Epidemiology and Microbiology. The results are published in the International Journal of Molecular Sciences.