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Article: Reactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1
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TitleReactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1
 
AuthorsWu, Z1
Liu, Q3
Liang, X1
Yang, X1
Wang, N4
Wang, X2
Sun, H2
Lu, Y4
Guo, Z1
 
KeywordsAntitumor drug
Copper transporter
Human copper transporter 1
Resistance
Uptake
 
Issue Date2009
 
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htm
 
CitationJournal Of Biological Inorganic Chemistry, 2009, v. 14 n. 8, p. 1313-1323 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00775-009-0576-7
 
AbstractCellular uptake of platinum-based antitumor drugs is a critical step in the mechanism of the drug action and associated resistance, and deeper understanding of this step may inspire development of novel methods for new drugs with reduced resistance. Human copper transporter 1 (hCtr1), a copper influx protein, was recently found to facilitate the cellular entry of several platinum drugs. In the work reported here, we constructed a Met- and His-rich 20mer peptide (hCtr1-N20) corresponding to the N-terminal domain of hCtr1, which is the essential domain of hCtr1 for transporting platinum drugs. The interactions of the peptide with cisplatin and its analogues, including transplatin, carboplatin, oxaliplatin, and [Pt(l-Met)Cl 2], were explored at the molecular level. Electrospray ionization (ESI) mass spectrometry (MS) data revealed that all of the platinum(II) complexes used in present study can bind to hCtr1-N20 in 1:1 and 2:1 stoichiometry. Four Met residues should be involved in binding to cis-platinum complexes on the basis of the tandem MS spectrometry and previously reported data. Time-dependent 2D [ 1H, 15N] heteronuclear single quantum coherence NMR spectra indicate the reaction of cisplatin with hCtr1-N20 is a stepwise process. The intermediate, however, is transient, which is consistent with the ESI-MS results. Time-dependent ESI-MS data revealed that the geometry and the properties of both the leaving and the nonleaving groups of platinum(II) complexes play essential roles in controlling the reactivity and formation of the final products with hCtr1-N20. © 2009 SBIC.
 
ISSN0949-8257
2013 Impact Factor: 3.164
 
DOIhttp://dx.doi.org/10.1007/s00775-009-0576-7
 
ISI Accession Number IDWOS:000271422100015
Funding AgencyGrant Number
National Natural Science Foundation of China20631020
90713001
20721002
Natural Science Foundation of Jiangsu ProvinceBK2008015
Funding Information:

Financial support from the National Natural Science Foundation of China (nos. 20631020, 90713001, and 20721002) and the Natural Science Foundation of Jiangsu Province (BK2008015) is gratefully acknowledged.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWu, Z
 
dc.contributor.authorLiu, Q
 
dc.contributor.authorLiang, X
 
dc.contributor.authorYang, X
 
dc.contributor.authorWang, N
 
dc.contributor.authorWang, X
 
dc.contributor.authorSun, H
 
dc.contributor.authorLu, Y
 
dc.contributor.authorGuo, Z
 
dc.date.accessioned2010-09-06T06:14:17Z
 
dc.date.available2010-09-06T06:14:17Z
 
dc.date.issued2009
 
dc.description.abstractCellular uptake of platinum-based antitumor drugs is a critical step in the mechanism of the drug action and associated resistance, and deeper understanding of this step may inspire development of novel methods for new drugs with reduced resistance. Human copper transporter 1 (hCtr1), a copper influx protein, was recently found to facilitate the cellular entry of several platinum drugs. In the work reported here, we constructed a Met- and His-rich 20mer peptide (hCtr1-N20) corresponding to the N-terminal domain of hCtr1, which is the essential domain of hCtr1 for transporting platinum drugs. The interactions of the peptide with cisplatin and its analogues, including transplatin, carboplatin, oxaliplatin, and [Pt(l-Met)Cl 2], were explored at the molecular level. Electrospray ionization (ESI) mass spectrometry (MS) data revealed that all of the platinum(II) complexes used in present study can bind to hCtr1-N20 in 1:1 and 2:1 stoichiometry. Four Met residues should be involved in binding to cis-platinum complexes on the basis of the tandem MS spectrometry and previously reported data. Time-dependent 2D [ 1H, 15N] heteronuclear single quantum coherence NMR spectra indicate the reaction of cisplatin with hCtr1-N20 is a stepwise process. The intermediate, however, is transient, which is consistent with the ESI-MS results. Time-dependent ESI-MS data revealed that the geometry and the properties of both the leaving and the nonleaving groups of platinum(II) complexes play essential roles in controlling the reactivity and formation of the final products with hCtr1-N20. © 2009 SBIC.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Biological Inorganic Chemistry, 2009, v. 14 n. 8, p. 1313-1323 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00775-009-0576-7
 
dc.identifier.citeulike5426744
 
dc.identifier.doihttp://dx.doi.org/10.1007/s00775-009-0576-7
 
dc.identifier.epage1323
 
dc.identifier.hkuros164212
 
dc.identifier.isiWOS:000271422100015
Funding AgencyGrant Number
National Natural Science Foundation of China20631020
90713001
20721002
Natural Science Foundation of Jiangsu ProvinceBK2008015
Funding Information:

Financial support from the National Natural Science Foundation of China (nos. 20631020, 90713001, and 20721002) and the Natural Science Foundation of Jiangsu Province (BK2008015) is gratefully acknowledged.

 
dc.identifier.issn0949-8257
2013 Impact Factor: 3.164
 
dc.identifier.issue8
 
dc.identifier.openurl
 
dc.identifier.pmid19669174
 
dc.identifier.scopuseid_2-s2.0-70449529412
 
dc.identifier.spage1313
 
dc.identifier.urihttp://hdl.handle.net/10722/69506
 
dc.identifier.volume14
 
dc.languageeng
 
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htm
 
dc.publisher.placeGermany
 
dc.relation.ispartofJournal of Biological Inorganic Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subjectAntitumor drug
 
dc.subjectCopper transporter
 
dc.subjectHuman copper transporter 1
 
dc.subjectResistance
 
dc.subjectUptake
 
dc.titleReactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1
 
dc.typeArticle
 
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<contributor.author>Wang, X</contributor.author>
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Author Affiliations
  1. Nanjing University
  2. The University of Hong Kong
  3. Nanjing University of Finance and EcoNomics
  4. University of Illinois at Urbana-Champaign