Institute of
bioorganic chemistry

A new structural group of antibiotics produced by a new strain Streptomyces sp. KMM 9044 was discovered as a result of teamwork of scientists from the Institute of Bioorganic Chemistry (IBCh RAS) and the Elyakov Pacific Institute of Bioorganic Chemistry (TIBOCh RAS). During the cultivation of the strain in the marine environment, two compounds with antibacterial activity were isolated. The structure of these compounds was established using the NMR and HRMS methods and also confirmed by a series of chemical transformations. The family of new compounds are chlorinated cyclic depsiheptapeptides containing 3-hydroxy-4-chlorvaline and 4-acetoxy-5-methylproline, non-standard amino acids in the depsipeptide macrocyclic structure and a glyceric acid residue. An interesting property of these antibiotics is the strong selective inhibition of a number of Gram-positive bacteria: Micrococcus sp., Arthrobacter sp., and Mycobacterium smegmatis. The results are published in Organic Letters. Learn more

Plant lignans are active components of many herbs, which makes them the research objects for therapeutic agents development for practical use. They provide diverse naturally-occurring pharmacophores, which allows them to interact with various enzymes, receptors, ion channels and signaling molecules. A team of scientists from IBCh RAS published a review that summarizes the comprehensive knowledge about lignan use as a bioactive compounds in disorders associated with oxidative stress and inflammation, pharmacological effects in vitro and in vivo, molecular mechanisms underlying these effects, and chemical synthesis approaches. The work is published in the International Journal of Molecular Sciences. Learn more

Recently, a team of scientists from the Laboratory of molecular oncology IBCH RAS together with the colleagues from other Russian Institutes uncovered that human telomerase RNA, which was considered non-coding, has a coding potential. In human cells, there are several isoforms of the telomerase RNA transcript, and hTERC gene expression are not silenced when telomerase is inactivated. Authors hypothesized that the biogenesis of the primary transcript should determine the function of the end product of human telomerase RNA gene expression. Analyzing the influence of various factors of RNA biogenesis on the processing and transport of human telomerase RNA, scientists found that an elongated form of human telomerase RNA (mRNA encoding the previously identified hTERP protein) accumulates in the cytoplasm when mechanism of degradation of polyadenylated RNAs is inhibited. The results are published in the Biomedicines.

Neurotrophins and their receptors regulate the differentiation, survival, and growth of nerve cells. Despite their central role in the life of neurons, the mechanisms underlying signal transmission into the cell are still not fully understood. According to one of the main hypotheses, after ligand binding the dimer of a Trk neurotrophin receptor undergoes a series of rearrangements that trigger signaling cascades inside the cell. However, structural data supporting this idea have not yet been available. Researchers from the Laboratory of Biomolecular NMR Spectroscopy of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, and the Institute of Biomedicine in Valencia have discovered two states of the transmembrane domain, which, apparently, are responsible for the active and inactive states of the receptor. In addition, it turned out that the extracellular juxtamembrane region is intrinsically disordered. The obtained data suggested that signal transduction is possible if the ligand binds directly to this receptor site, thereby stabilizing it. The work was published in iScience.

This is a collaborative work of researchers from the Laboratory of Biopharmaceutical Technologies of the IBCh RAS and Biological Testing Laboratory of the BIBCh RAS. Its goal is the development and testing of new anticoagulants from haematophagous organisms. Haemadin from the leech Haemadipsa sylvestris, variegin from the tick Amblyomma variegatum, and anophelin from Anopheles albimanus were chosen as the most promising anticoagulants. We have developed a method for the biotechnological production of these recombinant peptides with pharmaceutical purity. As a reference standard, we have used the recombinant hirudin-1 from Hirudo medicinalis (desirudin), which is the active substance of the FDA-approved drug Iprivask (Aventis Pharmaceuticals, USA). The anticoagulant activities of these peptides were compared using the thrombin amidolytic activity assay and detection of the prolongation of coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time) in mouse and human plasma. The article was published in the journal Biomedicines (IF 6.081).