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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

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
Authors
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
Citation
Journal Of Biological Inorganic Chemistry, 2009, v. 14 n. 8, p. 1313-1323 How to Cite?
Abstract
Cellular 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.
Persistent Identifierhttp://hdl.handle.net/10722/69506
ISSN
2013 Impact Factor: 3.164
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorWu, Zen_HK
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorLiang, Xen_HK
dc.contributor.authorYang, Xen_HK
dc.contributor.authorWang, Nen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorSun, Hen_HK
dc.contributor.authorLu, Yen_HK
dc.contributor.authorGuo, Zen_HK
dc.date.accessioned2010-09-06T06:14:17Z-
dc.date.available2010-09-06T06:14:17Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Biological Inorganic Chemistry, 2009, v. 14 n. 8, p. 1313-1323en_HK
dc.identifier.issn0949-8257en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69506-
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.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htmen_HK
dc.relation.ispartofJournal of Biological Inorganic Chemistryen_HK
dc.subjectAntitumor drugen_HK
dc.subjectCopper transporteren_HK
dc.subjectHuman copper transporter 1en_HK
dc.subjectResistanceen_HK
dc.subjectUptakeen_HK
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 1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0949-8257&volume=14&spage=doi: 10.1007/s00775&epage=009&date=2009&atitle=Reactivity+of+platinum-based+antitumor+drugs+towards+a+Met-+and+His-rich+20mer+peptide+corresponding+to+the+N-terminal+domain+of+human+copper+transporter+1en_HK
dc.identifier.emailSun, H:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00775-009-0576-7en_HK
dc.identifier.pmid19669174en_HK
dc.identifier.scopuseid_2-s2.0-70449529412en_HK
dc.identifier.hkuros164212en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70449529412&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume14en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1313en_HK
dc.identifier.epage1323en_HK
dc.identifier.isiWOS:000271422100015-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridWu, Z=40162703200en_HK
dc.identifier.scopusauthoridLiu, Q=24465353800en_HK
dc.identifier.scopusauthoridLiang, X=37044090600en_HK
dc.identifier.scopusauthoridYang, X=7406503159en_HK
dc.identifier.scopusauthoridWang, N=9738477800en_HK
dc.identifier.scopusauthoridWang, X=22036760200en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.scopusauthoridLu, Y=26643070000en_HK
dc.identifier.scopusauthoridGuo, Z=7404658029en_HK
dc.identifier.citeulike5426744-

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