Effect of trans-diamminedichloroplatinum(II) on human serum albumin: Conformational changes through partial disulfide bond cleavage

Novel Adducts of the Anticancer Drug Oxaliplatin with Glutathione and Redox Reactions with Glutathione Disulfide

“…Such redox chemistry of platinum() anticancer drugs has received relatively little previous attention. Lempers [36] and they also found that GSH reacts with cisplatin 17 times faster than with GSSG, and six times faster with the monoaqua adducts. [37] Further work is needed to elucidate the mechanism of such redox reactions.…”

Human serum albumin: spectroscopic studies of the paclitaxel binding and proximity relationships with cisplatin and adriamycin

“…Albumin may have a considerable impact on the activity of anti-cancer drug, including the most popular anthracycline drug adriamycin [28], and of platinum anti-tumour compounds [12,13]. The anthracycline binding to HSA has been reported to be a non-specific one [17], cisplatin binding takes place at Cys 34 and more likely at Met 298 [14,29].…”

“…Upon cisplatin coordination the a-helix structure was reduced about 10%, while the b-sheet increased about 10% [33]. A decrease of a-helix content was higher when trans-isomer was bound [13]. Our previous investigations [24] indicated that binding of paclitaxel to albumin impact on protein structure and it influences considerably albumin binding to other molecules like warfarin and bilirubin.…”

“…The reaction of cis-DDP with HSA attracts attention, because the protein binding may decrease the effective concentration of the free drug, which is responsible for anti-tumor activity [12]. Previous studies [13] have demonstrated that the interactions of cis-DDP with HSA causes distinct variations in protein conformation including a considerable decrease of the helical structure and a change of HSA binding abilities towards other molecules. Possible albumin binding site for cisplatin appears to be not only Cys 34, but also {S,N} macrochelate involving Met 298 [14] (Scheme 1).…”

Determination of Pt–DNA adducts and the sub-cellular distribution of Pt in human cancer cell lines and the leukocytes of cancer patients, following mono- or combination treatments, by inductively-coupled plasma mass spectrometry

“…thiols, carbonyl oxygens and amino nitrogens) such as human serum albumin, one of the most abundant proteins in blood plasma [43][44][45][46][47][48]. These reactions partially inactivate the drugs and reduce their subcellular uptake.…”