کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8327000 | 1540198 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ligand-induced glutathione transferase degradation as a therapeutic modality: Investigation of a new metal-mediated affinity cleavage strategy for human GSTP1-1
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Glutathione transferases (GST, EC. 2.5.1.18) are overexpressed in cancer cell and have been shown to be involved in cancer cell growth, differentiation and the development of multi-drug resistance (MDR) mechanism. Therefore, GST inhibitors are emerging as promising chemosensitizers to manage and reverse MDR. The present work aims to the synthesis, characterization and assessment of a new active-site chimeric inhibitor towards the MDR-involved human GSTP1-1 isoenzyme (hGSTP1-1). The inhibitor [BDA-Fe(III)] was designed to possess two functional groups: the anthraquinone moiety, as recognition element by hGSTP1-1 and a metal chelated complex [iminodiacetic acid-Fe(III)] as a reactive moiety, able to generate reactive oxygen species (ROS), through Fenton reaction. Upon binding of the BDA-Fe(III) to hGSTP1-1 in the presence of hydrogen peroxide, reactive oxygen species (ROS) are generated, which promoted the specific cleavage of hGSTP1-1 in a time and concentration-dependent manner. Electrophoretic analysis showed that each enzyme subunit is cleaved at a single site. Amino acid sequencing as well as molecular modelling studies established that the cleaved peptide bond is located between the amino acids Tyr103 and Ile104. This ligand-induced hGSTP1-1 degradation and inactivation strategy is discussed as a new approach towards chemosensitization of MDR cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 116, September 2018, Pages 84-90
Journal: International Journal of Biological Macromolecules - Volume 116, September 2018, Pages 84-90
نویسندگان
Mohammed Hamed Alqarni, Magdy Mohamed Muharram, Nikolaos E. Labrou,