Registration Number
0214U006949,
0113U006029
, R & D reports
Title
Development of target based methodology of rational search for new antituberculous medicinal preparation.
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Head
Tukalo Mykhaylo, Доктор біологічних наук
Registration Date
15-04-2014
Organization
Institute of Molecular Biology and Genetics of NASU
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The homology model of three-dimensional structure of prolyl-tRNA synthetase (ProRS) M. tuberculosis has been built. The method of receptor-oriented virtual screening has been proposed and docking collection of the library comprising 100,000 compounds into active site of ProRS M. tuberculosis were performed. Recombinant LeuRS M. tuberculosis has been obtained in amount of 50 mg and purified to >95%. The protocols of biochemical testing of inhibitory activity for chemical compounds toward LeuRS M. tuberculosis have been proposed and 408 compounds, selected during receptor-oriented virtual screening, have been tested under 1 mM and 100 µM compound concentrations. Based on the residual activity of enzyme for further investigations we have selected 15 the most promising compounds. The IC50 values were calculated for 6 inhibitors in both aminoacylation and ATP-pyrophosphate exchange reactions. The best values of IC50 were 6, 7.2 and 7.6 µM in aminoacylation reaction, and 1.9, 11.4 and 12.8 µM in ATP-pyrophosphate exchange reaction.
Product Description
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Бджола Володимир Григорович
Бояршин Костянтин Сергійович
Волинець Галина Петрівна
Грищенко Андрій Анатолійович
Гудзера Ольга Йосипівна
Кpикливий Iван Андрійович
Коваленко Оксана Петрівна
Лукашов Сергій Степанович
Остринська Ольга Василівна
Яpемчук Ганна Дмитрівна
Ярмолюк Сергій Миколайович
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2020-04-02
