Laboratory of Biological Testing

Today the Laboratory of Biological Testing is the most titled in the Russian Federation in the field of non-clinical research. Since 2005, it has been accredited by Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). In 2013, the Laboratory was officially recognized as conforming to the principles of good laboratory practice (GLP) by the Slovak National Accreditation Service (SNAS), which allows us to declare that the results of non-clinical studies carried out in it can be recognized in the countries of the Organization for Economic Cooperation and Development (EU countries, USA, Canada, etc.). In addition, the Laboratory was the first laboratory that received recognition of compliance with GLP principles by the Russian monitoring agency – the Federal Accreditation Service, and therefore the work on the creation of the National GLP system was completed in Russia.

Now the Laboratory together with MIPT and the Research Institute of Medical Primatology organized two geographically remote platforms. Thus, a center was formed that performs a full cycle of non-clinical studies in accordance with the principles of GLP. Thanks to this center in Russia, it was possible to export both the products that were examined in this center and services for non-clinical research for foreign customers, and also participate in complex international programs on the study of medicines, pesticides, cosmetic products, veterinary drugs, food and fodder additives, industrial chemicals.

 

All publications (show selected)

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Igor Dyachenko

The physiological effect of two bisbenzylisoquinoline alkaloids having activity on ASIC1a

In collaboration with Laboratory of bioengineering of neuromodulators and neuroreceptors,  Laboratory of neuroreceptors and neuroregulators

The ASIC1a is the most sensitive subtype of acid-sensing ion channel in the cell membrane, and it plays an important role in the excitation of neurons of CNS. Long time the ligands to this ASIC subtype are under intense attention for the development of drugs for pain relief, as well as protectors from strokes and neurodegenerative diseases. In in vitro experiments on heterologically expressed ASIC1a channels, the action of two bisbenzylisoquinoline alkaloids from plants was studied by electrophysiological method of two-electrode potential fixing on oocyte cells.

The alkaloid lindoldhamine extracted from the leaves of Laurus nobilis L. significantly inhibited the ASIC1a channel’s response to physiologically-relevant stimuli of pH 6.5–6.85 with IC50 range 150–9 µM, but produced only partial inhibition of that response to more acidic stimuli. In mice, the intravenous administration of lindoldhamine at a dose of 1 mg/kg significantly reversed complete Freund’s adjuvant-induced thermal hyperalgesia and inflammation; however, this administration did not affect the pain response to an intraperitoneal injection of acetic acid. Thus, it was shown not only a prospective of plant alkaloids using for a pain relief, but was indirectly confirmed the involvement of the ASIC1a channels of the peripheral nervous system in the generation of a pain response to mild acidification.

The structural analogue named daurisoline, unlike lindoldamine, did not inhibit the activation of the ASIC1a channel by protons, but produced the second peak component of the ASIC1a current. This second peak manifested with a 2.5 seconds delay after the first fast respond followed by completely desensitization with the same kinetics as the main peak. The presence of second current components was specific characteristic of ASIC2 and ASIC3 subtypes early, but this component is sustained, that last all time while the acid stimulus presented. The discovery of the second component of ASIC1a current allows us to declare the common mechanism of opening and desensitization for all ASICs, which will be interesting to determine in further experiments.

Development of efficient solid-phase synthesis methods for the preparation of peptides that possess immunosuppresive activity

In collaboration with Laboratory of pharmacokinetics,  Group of Peptide Chemistry

The relative efficacies of several synthesis methods have been investigated aiming to prepare target peptides that are quite potent in a test for suppression of the experimental autoimmune encephalomyelitis. Toward this goal chemical yields of the target peptides as well as side product distributions in the samples of the peptides obtained using various methods have been evaluated and quantitatively characterized. A variation of Fmoc/tBu methodology have been found to be the most efficient providing targets peptides in the highest chemical yield since it allowed to use a broader range of  activated amino acid derivatives. Side products of the amino acid doubling were detected among the side products of chemical synthesis. Some of the amino acid doubling side products made the HPLC purification step to be complicated. Nevertheless the synthetic methods developed allowed the preparation of the target peptides in sufficient quantities.

Development of peptide drugs for the treatment of multiple sclerosis

In collaboration with Laboratory of hormonal regulation proteins,  Group of Peptide Chemistry,  Laboratory of pharmacokinetics

Multiple sclerosis is a chronic autoimmune disease with neurological pathology. The dominant role of immunological processes in the development of the disease dictates the need for medications that specifically minimize the activity of immune processes. The peptides A8AMS and mA8AMS, homologous to the fragment of the human IgG VH domain, have been shown to act in vitro and in vivo, effectively reducing the symptoms of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The results provide new opportunities for the development of peptide drugs for the treatment of multiple sclerosis.