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Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.

Publication ,  Journal Article
Crider, SE; Holbrook, RJ; Franz, KJ
Published in: Metallomics : integrated biometal science
January 2010

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 via proteins. 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.

Duke Scholars

Published In

Metallomics : integrated biometal science

DOI

EISSN

1756-591X

ISSN

1756-5901

Publication Date

January 2010

Volume

2

Issue

1

Start / End Page

74 / 83

Related Subject Headings

  • Peptides
  • Organoplatinum Compounds
  • Norleucine
  • Molecular Sequence Data
  • Molecular Sequence Annotation
  • Methionine
  • Mass Spectrometry
  • Humans
  • Copper Transporter 1
  • Chromatography, Liquid
 

Citation

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Crider, S. E., Holbrook, R. J., & Franz, K. J. (2010). Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1. Metallomics : Integrated Biometal Science, 2(1), 74–83. https://doi.org/10.1039/b916899k
Crider, Sarah E., Robert J. Holbrook, and Katherine J. Franz. “Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.Metallomics : Integrated Biometal Science 2, no. 1 (January 2010): 74–83. https://doi.org/10.1039/b916899k.
Crider SE, Holbrook RJ, Franz KJ. Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1. Metallomics : integrated biometal science. 2010 Jan;2(1):74–83.
Crider, Sarah E., et al. “Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.Metallomics : Integrated Biometal Science, vol. 2, no. 1, Jan. 2010, pp. 74–83. Epmc, doi:10.1039/b916899k.
Crider SE, Holbrook RJ, Franz KJ. Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1. Metallomics : integrated biometal science. 2010 Jan;2(1):74–83.
Journal cover image

Published In

Metallomics : integrated biometal science

DOI

EISSN

1756-591X

ISSN

1756-5901

Publication Date

January 2010

Volume

2

Issue

1

Start / End Page

74 / 83

Related Subject Headings

  • Peptides
  • Organoplatinum Compounds
  • Norleucine
  • Molecular Sequence Data
  • Molecular Sequence Annotation
  • Methionine
  • Mass Spectrometry
  • Humans
  • Copper Transporter 1
  • Chromatography, Liquid