An Investigation into the Essential Residues in the Interaction Between Cisplatin and the CTerminus of hCTR1
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Cisplatin has been used as an anti cancer agent for many years. However, the exact mechanism for the cellular uptake of cisplatin is still not completely understood. Research into the involvement of the protein Human Copper Transporter 1 in the uptake process was performed, focusing in particular on the carboxy-terminus to determine the essential residues in the interaction with cisplatin. Ultraviolet spectroscopy, two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry were all utilized in the investigation. The major binding sites were found to be the cysteine residue and terminal ammine of the peptide, with the peptide being singly platinated at low cisplatin concentrations and bis-platinated or tris-platinated at high cisplatin concentrations. These results suggest that the cisplatin initially binds to the cysteine residue and is then transferred within the peptide to the terminal ammine binding site to allow for further platination. With an improved understanding of cisplatin’s interaction with Human Copper Transporter 1, more methods of overcoming the drug delivery obstacle can be introduced.