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Registration Number

0223U003547, 0117U002878 , R & D reports

Title

Study of nanocomposite protein complexes of the translation apparatus of higher eukaryotes TyrRS, EMAP II and AIMP / p43: fundamental and applied aspects

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Head

Kornelyk Olexandr I., Доктор біологічних наук

Registration Date

24-05-2023

Organization

Institute of Molecular Biology and Genetics of NAS of Ukraine

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Fundamental and applied aspects of the creation of nanocomposite complexes of the translation apparatus proteins the EMAP II, AIMP/p43 and C-modul of tyrosyl-tRNA synthetase, which are multifunctional proteins and have cytokine functions, were studied. For the first time, the spatial structure of the cytokine EMAP II in solution was determined by the methods of multidimensional NMR spectroscopy, and the high conformational mobility of the RNA-binding motif was revealed. For the first time, a temperature-stable complex of cytokine EMAP II with dextran-70 was created and its stimulating effect on tumor necrosis factor production was shown, as well as a significant enhancement of the antitumor activity of EMAP II on human prostate adenocarcinoma xenografts in mice. An experimental study of EMAP II and AIMP1/p43 cytokine complexes with TiO2 nanoparticles showed the ability of TiO2 nanoparticles to stabilize these proteins and prevent the formation of their high molecular weight aggregates. A complex mechanism of the pattern-dose-dependent cytotoxic effect of the EMAP II protein on glioma cells in primary culture obtained from patients, as well as on the culture of human glioma cells U251 GM, was established, which may be the result of the multifunctionality of this protein and its ability to interact with different receptors. . Due to the combined effect of EMAP II and isatizone on the culture of MSF-7 cells, an increased inhibition of the proliferation of malignant cells and the initiation of apoptosis was obtained. After the combined use of the xenogenic antitumor vaccine, developed at the Institute named after RE Kavetsky NAS of Ukraine, with the drug isatisone in the Lewis lung carcinoma model the number of metastatic lesions in the lungs of experimental animals decreased almost 10 times.

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Bolsunova Olga Igorevna
Zaika Leonid A.
Zadorozhnii Borys О.
Karpova Iryna S.
Katsan Valentyna A.
Kolomiiets Lesia Igorivna
Lylo Valentyna V.
Lozhko Dmytro M.
Potopalskyi Anatolii I.
Savytskyi Oleksandr V.
Shuba Irina M

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2023-05-24