Interaction between Platinum Complexes and the C-Terminal Motif of Human Copper Transporter 1

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• 作者：Erqiong Wang ; Zhaoyong Xi ; Yan Li ; Lianzhi Li ; Linhong Zhao ; Guolin Ma ; Yangzhong Liu
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：May 20, 2013
• 年：2013
• 卷：52
• 期：10
• 页码：6153-6159
• 全文大小：331K
• 年卷期：v.52,no.10(May 20, 2013)
• ISSN：1520-510X

文摘

Human copper transporter 1 (hCTR1) facilitates the cellular uptake of cisplatin, and the extracellular N-terminal domain has been proven to coordinate to platinum drugs. It has been reported that the intracellular C-terminal motif is crucial for the function of hCTR1 in cisplatin influx. In this work, we conduct reactions of the intracellular motif with platinum drugs. The octapeptide from the C-terminal domain of hCTR1 is used, and the reactions are investigated using ultraviolet, high-performance liquid chromatography, electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy. Results show that the C8 peptide is highly reactive to cisplatin and oxaliplatin, and the -HCH sequence is the most favorable binding site of platinum agents. Cisplatin first binds to the cysteine residues in the reaction with the C8 peptide. The ammine ligand, even trans to a thiol ligand, can remain coordinated in platination adducts for a >12 h reaction. Intramolecular platinum migration was observed in the C8 peptide, and the ammine ligands remain coordinated to platinum during this process. This result indicates that hCTR1 can transfer cisplatin in the active form through a trans chelation process. These findings provide insight into the mechanism of the C-terminus of hCTR1 in the transfer of platinum drugs from the trimeric pore of hCTR1 to the cytoplasm.