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Article: Activation of carboplatin and nedaplatin by the N-terminus of human copper transporter 1 (hCTR1)

TitleActivation of carboplatin and nedaplatin by the N-terminus of human copper transporter 1 (hCTR1)
Authors
KeywordsAnticancer compounds
Anticancer drug
Bidentate ligands
Blood plasma
Carboplatin
Issue Date2012
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp
Citation
Chemical Science, 2012, v. 3 n. 11, p. 3206-3215 How to Cite?
AbstractHuman copper transporter 1 (hCTR1) is a major copper uptake protein. Interestingly, it also mediates the uptake of selected platinum (Pt) anticancer drugs such as cisplatin and carboplatin. Here we studied the interactions of the N-terminus of hCTR1 (hCTR1-N) with carboplatin and its analogue nedaplatin by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Our 2D [ 1H, 15N] SOFAST-HMQC NMR data demonstrated that hCTR1-N binds to these Pt drugs through methionine residues to form ring-opened monofunctional adducts. Such a binding significantly activated these platinum drugs. High resolution ESI-MS spectra showed that a maximum of two Pt atoms bound per monomer of the protein for carboplatin and nedaplatin in a similar manner to cisplatin. In contrast, transplatin interacted with hCTR1-N more rapidly, yielding a different binding species with a maximum of five transplatin bound per monomer of the protein. The nucleophiles in serum, e.g. chloride and bicarbonate, can also play a role in the pre-activation of carboplatin and nedaplatin in the blood plasma prior to reaching their cellular targets. This study provides an insight into the possible mechanism of in vivo activation of Pt anticancer compounds with bidentate ligands. © 2012 The Royal Society of Chemistry.
Persistent Identifierhttp://hdl.handle.net/10722/159380
ISSN
2014 Impact Factor: 9.211
2014 SCImago Journal Rankings: 4.455
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_US
dc.contributor.authorLi, Hen_US
dc.contributor.authorDu, Xen_US
dc.contributor.authorHarris, Jen_US
dc.contributor.authorGuo, Z-
dc.contributor.authorSun, H-
dc.date.accessioned2012-08-16T05:48:57Z-
dc.date.available2012-08-16T05:48:57Z-
dc.date.issued2012en_US
dc.identifier.citationChemical Science, 2012, v. 3 n. 11, p. 3206-3215en_US
dc.identifier.issn2041-6520en_US
dc.identifier.urihttp://hdl.handle.net/10722/159380-
dc.description.abstractHuman copper transporter 1 (hCTR1) is a major copper uptake protein. Interestingly, it also mediates the uptake of selected platinum (Pt) anticancer drugs such as cisplatin and carboplatin. Here we studied the interactions of the N-terminus of hCTR1 (hCTR1-N) with carboplatin and its analogue nedaplatin by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Our 2D [ 1H, 15N] SOFAST-HMQC NMR data demonstrated that hCTR1-N binds to these Pt drugs through methionine residues to form ring-opened monofunctional adducts. Such a binding significantly activated these platinum drugs. High resolution ESI-MS spectra showed that a maximum of two Pt atoms bound per monomer of the protein for carboplatin and nedaplatin in a similar manner to cisplatin. In contrast, transplatin interacted with hCTR1-N more rapidly, yielding a different binding species with a maximum of five transplatin bound per monomer of the protein. The nucleophiles in serum, e.g. chloride and bicarbonate, can also play a role in the pre-activation of carboplatin and nedaplatin in the blood plasma prior to reaching their cellular targets. This study provides an insight into the possible mechanism of in vivo activation of Pt anticancer compounds with bidentate ligands. © 2012 The Royal Society of Chemistry.-
dc.languageengen_US
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.aspen_US
dc.relation.ispartofChemical Scienceen_US
dc.subjectAnticancer compounds-
dc.subjectAnticancer drug-
dc.subjectBidentate ligands-
dc.subjectBlood plasma-
dc.subjectCarboplatin-
dc.titleActivation of carboplatin and nedaplatin by the N-terminus of human copper transporter 1 (hCTR1)en_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=2041-6520&volume=3&spage=&epage=&date=2012&atitle=Activation+of+carboplatin+and+nedaplatin+by+the+N-terminus+of+human+copper+transporter+1+(hCTR1)en_US
dc.identifier.emailLi, H: hylichem@hku.hken_US
dc.identifier.emailSun, H: hsun@hku.hken_US
dc.identifier.authoritySun, H=rp00777en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1039/c2sc20738aen_US
dc.identifier.scopuseid_2-s2.0-84867342140-
dc.identifier.hkuros205086en_US
dc.identifier.volume3en_US
dc.identifier.issue11-
dc.identifier.spage3206-
dc.identifier.epage3215-
dc.identifier.eissn2041-6539-
dc.identifier.isiWOS:000311068100012-
dc.publisher.placeUnited Kingdom-

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