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Issue 1, 2010
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Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1

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Abstract

Platinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport viaproteins. The copper transport protein Ctr1 is responsible for high affinity copper uptake but has also been implicated in the transport of cisplatin into cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular N-terminus that are potential platinum-binding sites: the first one encompasses residues 7–14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the second one spans residues 39–46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In these studies, we use liquid chromatography and mass spectrometry to compare the binding interactions between cisplatin, carboplatin and oxaliplatin with synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of cisplatin and carboplatin with Met-rich motifs that contain three or more methionines result in removal of the carrier ligands of both platinum complexes. In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum coordination to the peptide.

Graphical abstract: Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1

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Publication details

The article was received on 17 Aug 2009, accepted on 23 Oct 2009 and first published on 02 Nov 2009


Article type: Paper
DOI: 10.1039/B916899K
Citation: Metallomics, 2010,2, 74-83
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    Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1

    S. E. Crider, R. J. Holbrook and K. J. Franz, Metallomics, 2010, 2, 74
    DOI: 10.1039/B916899K

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