Design and screening of high-affinity ligands for glutathione S-transferase as fusion tag
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Design and screening of high-affinity ligands for glutathione S-transferase as fusion tag
Journal of Chongqing Medical UniversityVol. 37, Issue 9, Pages: 791-795(2012)
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重庆医科大学检验医学院临床检验诊断学教育部重点实验室,重庆,400016
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Published:2012,
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YANG Xianfeng, ZHANG Ling, YANG Xiaolan, et al. Design and screening of high-affinity ligands for glutathione S-transferase as fusion tag. [J]. Journal of Chongqing Medical University 37(9):791-795(2012)
DOI:
YANG Xianfeng, ZHANG Ling, YANG Xiaolan, et al. Design and screening of high-affinity ligands for glutathione S-transferase as fusion tag. [J]. Journal of Chongqing Medical University 37(9):791-795(2012)DOI:
Design and screening of high-affinity ligands for glutathione S-transferase as fusion tag
Objective:To design and screen high-affinity ligands for schistosoma japonicum glutathione S-transferase(GST) as fusion tag. Methods:pGST-MOLUC was induced to express GST in Escherichia coli BL21 under low temperature and GST was purified by glutathione Sepharose 4B affinity chromatography. By the initial velocity method,Km of GST aganist glutathione(GSH) and 1-chloro-2,4-dinitrobenzene(CDNB) was estimated. S-(2,4-dinitrobenzne)-glutathione(GS-DNB),3,5-dimethylbenzoic acid,4-butylben-zoic acid and ethacrynic acid were tested and the inhibition etfect of symmetrical biamide of such aromatic carboxylic acid on GST was examed. Results:Homogenous GST was successfully obtained. GSH and CDNB followed sequential bisubstrate kinetic mechanism with both Km over 0.10 mmol/L. GS-DNB had a competitive Ki of about 5.0 μmol/L against CDNB but a noncompetitive Ki of about 33 μmol/L against GSH. 3,5-dimethylbenzoic acid,4-butylbenzoic acid,and ethacrynic acid showed Ki over 0.20 mmol/L,but N,N’-bis-ethacrynyl-1,4-butyldiamine and N,N’-bis-(4-(n-butyl)-benzoyl)-1,4-butyldiamine displayed strong competitive inhibition on this GST against GSH with Ki of 31 nmol/L and (0.61±0.43) μmol/L(n=3),correspondingly. Conclusion:Symmetrical biamide of low-affinity aromatic carboxylic acid linked via short linear chain has promise to be high-affinity inhibitors to single active site of GST.