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Trypanosoma cruzi is a parasite causing Chagas disease, which is nowadays treated with only two drugs: benznidazole and nifurtimox. However, these drugs are effective only in the early or acute infection phases and have side effects. It should be added that about 7 million people all over the world suffer from the disease and thus the development of new drugs against Chagas disease is a significant task. The action of new drugs may be based on their inhibitory effect on the biosynthesis of compounds vital for the parasite, for example vitamin C (antioxidant). Galactonolactone oxidase from Trypanosoma Cruzi (TcGAL) is an enzyme which catalysis the final stage of the biosynthesis vitamin C and so the inhibition of TcGAL may be suitable way to suppress the growth of the parasite. However, the development of a technique for the analysis of activity and, so, the search for an effective inhibitor of the enzyme has been impossible until now due to its membranotropic nature and, accordingly, the tendency to aggregate in aqueous solutions. Thus, the expression of the recombinant enzyme TcGAL from Trypanosoma cruzi in E. coli cells leads to the formation of an aggregated and inactive protein, the so-called inclusion bodies. Attempts to restore the catalytic function of TcGAL using various methods traditionally used for enzyme refolding have not been successful. In this project, an innovative technology has been developed for obtaining genetically engineered TcGAL in a soluble and catalytically active form using a system of reverse micelles of surfactants. The developed approach makes it possible to create a high-throughput screening system for the search for a selective TcGAL inhibitor, on the basis of which it is possible to conduct a targeted search for new drugs against diseases caused by trypanosomal infection.
№ | Имя | Описание | Имя файла | Размер | Добавлен |
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1. | Preconf_bionanotox_full_abstract_book.pdf | Preconf_bionanotox_full_abstract_book.pdf | 1,2 МБ | 31 мая 2022 [Andrew_18] |