title: Interaction between platinum complexes and the C-terminal motif of human copper transporter 1.
abstract: 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.
authors: CAS Key Laboratory of Soft Matter Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei Anhui 230026, China.
authors: Erqiong
authors: E
authors: Wang
authors: Zhaoyong
authors: Z
authors: Xi
authors: Yan
authors: Y
authors: Li
authors: Lianzhi
authors: L
authors: Li
authors: Linhong
authors: L
authors: Zhao
authors: Guolin
authors: G
authors: Ma
authors: Yangzhong
authors: Y
authors: Liu
mesh_terms: D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism; D000079923:Copper Transporter 1; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism; D000077150:Oxaliplatin
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D009842:Oligopeptides; D009944:Organoplatinum Compounds; C490079:SLC31A1 protein, human; D000077150:Oxaliplatin; D002945:Cisplatin