Toward a better understanding of the oxaliplatin mode of action upon the steric hindrance of 1,2-diaminocyclohexane and its analogue.
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.
['Wang|Zhimei|Z|', 'Wu|Mian|M|', 'Gou|Shaohua|S|']
D000970:Antineoplastic Agents D002851:Chromatography, High Pressure Liquid D003514:Cyclohexylamines D005978:Glutathione D009944:Organoplatinum Compounds D000077150:Oxaliplatin
Oxaliplatin Steric hindrance Guanosine Glutathione