We have reacted several derivatives of the anticancer drug cisplatin with N-acetyl-L-cysiene (N-AcCys) and N-acetyl-L-methionine (N-AcMet), which are two of the primary amino acid targets of platinum. NMR spectroscopy was used to monitor the reactions and determine the effects the different ligands would have on the platinum reactivity. For several of the platinum compounds we tested them at pH 4 and 7, and with platinum:amino acid ratios of 1:1, 1:2, 2:1. We also did competitiion reactions between cystiene and methionine. [Pt(dien)(NO3)]+ reacts faster with methionine with cysteine at both pH 4 and 7 at a 1:1:1 ratio. [Pt(N,N,N',N',N''-pentamethyldiethylenetriamine)(NO3)]+ reacts with methionine faster at pH 4 but with cystiene at pH 7. This is most likely due to the thiol in the cystiene starting to deprotenate around pH 7. [Pt(Me4en)(NO3)2](Me4en = N,N,N',N'-tetramethylethylenediamine) forms several products with N-AcCys at both pH 4 and 7, with amounts of the products varying depending on the ratio of platinum and Cys. Mass spectrometry indicated one product as {[Pt(Me4en)(H2O)]2(N-AcCys)}2+, with two platinum compounds coordinated to a single cysteine.

Effects of carrier ligands on cispaltin analog binding to cysteine and methionine

253rd National Meeting (2017)

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