التفاصيل البيبلوغرافية
| العنوان: |
Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents |
| المؤلفون: |
Larsson, Anna-Karin, Shokeer, Abeer, Mannervik, Bengt |
| المصدر: |
Archives of Biochemistry and Biophysics. 497(1-2):28-34 |
| مصطلحات موضوعية: |
Glutathione transferase (GST), 3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) Chloroethylnitrosoureas (CENUs), Directed evolution, Alkyltransferase, Alkylating agents, NATURAL SCIENCES, Chemistry, NATURVETENSKAP, Kemi |
| الوصف: |
Glutathione transferase (GST) displaying enhanced activity with the cytostatic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and structurally related alkylating agents was obtained by molecular evolution. Mutant libraries created by recursive recombination of cDNA coding for human and rodent Theta-class GSTs were heterologously expressed in Escherichia coli and screened with the surrogate substrate 4-nitrophenethyl bromide (NPB) for enhanced alkyltransferase activity. A mutant with a 70-fold increased catalytic efficiency with NPB, compared to human GST T1-1, was isolated. The efficiency in degrading BCNU had improved 170-fold, significantly more than with the model substrate NPB. The enhanced catalytic activity of the mutant GST was also 2-fold higher with BCNU than wild-type mouse GST T1-1, which is 80-fold more efficient than wild-type human GST T1-1. We propose that GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side-effects in treated patients, and as selectable markers in gene therapy. |
| وصف الملف: |
print |
| URL الوصول: |
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-119509 |
| قاعدة البيانات: |
SwePub |