کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1316886 | 1499430 | 2016 | 7 صفحه PDF | دانلود رایگان |
• Glutathione can compete with guanosine 5’′-monophosphate to bind the active platinum unit.
• Glutathione can substitute the guanine to form inactive platinum species.
• A suitable spatial moiety is needed in oxaliplatin derivative
• A suitable spatial moiety can prevent the binding of glutathione from Pt-DNA adduct.
The present research is concerned with the mechanism investigation on the interaction between oxaliplatin and guanosine 5′-monophosphate (GMP) in the presence of glutathione (GSH). The binding modes of oxaliplatin with GMP and GSH were explored by HPLC and LC–MS techniques, respectively, in which four key intermediates were found and five adducts were determined in the reaction. The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways. One is by competing with GMP to bind the active platinum unit, and the other is by substituting the guanine-N7 atom of DNA to form inactive platinum species. In contrast to oxaliplatin with trans 1,2-diaminocyclohexane as spatial framework, a known platinum(II) complex, characteristic of trans-bicyclo[2.2.2]octane-7,8-diamine possessing dicyclic steric hindrance, was also studied in the same way to explore its mode of action with DNA.
Glutathione (GSH) can disturb the reaction of oxaliplatin with DNA via replacing the guanine-N7 atom of DNA to form a ternary DNA–Pt–glutathione complex.Figure optionsDownload as PowerPoint slide
Journal: Journal of Inorganic Biochemistry - Volume 157, April 2016, Pages 1–7