Institute of
bioorganic chemistry

Dysregulation of post-translational modifications (PTMs) like phosphorylation is often involved in disease. NMR may elucidate exact loci and time courses of PTMs at atomic resolution and near-physiological conditions but requires signal assignment to individual atoms. Conventional NMR methods for this base on tedious global signal assignment that may often fail, as for large intrinsically disordered proteins (IDPs). We present a sensitive, robust alternative to rapidly obtain only the local assignment near affected signals, based on FOcused SpectroscopY (FOSY) experiments using selective polarisation transfer (SPT). We prove its efficiency by identifying two phosphorylation sites of glycogen synthase kinase 3 beta (GSK3β) in human Tau40, an IDP of 441 residues, where the extreme spectral dispersion in FOSY revealed unprimed phosphorylation also of Ser409. FOSY may broadly benefit NMR studies of PTMs and other hotspots in IDPs, including sites involved in molecular interactions.

Scientists from Laboratory of molecular immunology of IBCh RAS performed first broad comprehensive study of factors which influence degradation rate of magnetic particles in mammals. For this aim magnetic spectral approach was developed, allowing non-invasive and quantitative measurement of magnetic particles in mice without influence of biogenic iron. Researchers studied the key factors that determine the degradation rate of nanoparticles: particle dose, size, zeta potential, type of polymer coating and internal architecture of nanoagents. The revealed deeper insights into the particle degradation in vivo may facilitate rational design of theranostic nanoparticles with predictable long-term fate in vivo. The work was published in ACS Nano.

In the laboratory of molecular immunogenetics of cancer IGB RAS was demonstrated that the PGLYRP1/Tag7 innate immunity protein can be regarded as an inhibitor of TNFα cytotoxic activity via the interaction with its TNF receptor 1 (TNFR1). A C-terminal peptide fragment 17.1 of the molecule is responsible for this function. In this study was demonstrated that the minimal 8-mer region of this peptide (hereinafter – 17.1A) is capable to bind to TNFR1. As a result of such interaction, the cytotoxic signals induced by this receptor are blocked. In the Nursery for laboratory animals BIBCh RAS was demonstrates that this peptide an anti-inflammatory activity in vivo in the complete Freund’s adjuvant (CFA)-induced arthritis model in laboratory mice. Peptide 17.1A is capable to reduce periarticular inflammation, inhibit the development of synovitis and exhibit a protective effect on cartilage and bone tissues. The work was published in Frontiers in Immunology.

International research team together with researchers from IBCh RAS studied molecular mechanisms of histone acetyltransferase KAT8 activity. The enzyme regulates DNA compactization and gene transcription regulation by acetylation of histone H4 and is essential for cell viability. The results are published in the journal Molecular Cell. Learn more

Peptide synthesis is one of the hotspots of the Institute of Bioorganic Chemistry. Many of the Institute's key achievements are directly related to this area of work. One of the approaches to the synthesis of "die-hard" peptides is the use of serine, threonine and cysteine with special protection of side groups, which forms a five-membered heterocycle. Such derivatives of these amino acids are called "pseudoprolines" for their structural similarity to the corresponding amino acid. Usually, such protected amino acids are used in the form of dipeptides. Due to the low potential of the amino group to acylation, their one by one incorporation into the growing peptide chain is difficult. A recent article by the Department of Molecular Neuroimmune Signaling in the Amino Acids journal demonstrated the ability to synthesize "difficult" peptides using single derivatives of serine, threonine and cysteine in the form of protected pseudoprolines. This technical solution dramatically simplifies and reduces the cost of the synthesis of complex sequences compared to previously used dipeptide derivatives and makes such constructs generally available.