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dc.contributor.authorAng, Wee Han
dc.contributor.authorBrown, William Wesley
dc.contributor.authorLippard, Stephen J.
dc.date.accessioned2013-11-18T13:34:42Z
dc.date.available2013-11-18T13:34:42Z
dc.date.issued2009-04
dc.date.submitted2009-02
dc.identifier.issn1043-1802
dc.identifier.issn1520-4812
dc.identifier.urihttp://hdl.handle.net/1721.1/82151
dc.description.abstractFDA-approved platinum-based anticancer drugs, cisplatin, carboplatin, and oxaliplatin, are some of the most effective chemotherapies in clinical use. The cytotoxic action of these compounds against cancer requires a combination of processes including cell entry, drug activation, DNA binding, and transcription inhibition resulting in apoptotic cell death. The drugs form Pt lesions with nuclear DNA, leading to the arrest of key cellular functions and triggering a variety of cellular responses. DNA probes containing Pt−DNA conjugates are important tools for studying the molecular mechanisms of these processes. In order to facilitate investigation of specific Pt−DNA lesion processing within live cells, we devised a strategy for constructing plasmids containing a single site-specific Pt−DNA adduct. The method involves the use of nicking restriction enzymes to create closely spaced tandem gaps on the plasmid followed by removal of the intervening doubly nicked DNA strand to form a short single-stranded gap. Synthetic platinated oligonucleotides were incorporated into the gapped plasmid construct to generate a covalently closed circular platinated plasmid in good yield. We discuss the application of this methodology to prepare plasmids containing a platinum 1,2-d(G*pG*) or 1,3-d(G*pTpG*) intrastrand cross-link, two notable adducts formed by the three clinically approved drugs.en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (CA34992)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/bc900031aen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titlePreparation of Mammalian Expression Vectors Incorporating Site-Specifically Platinated-DNA Lesionsen_US
dc.typeArticleen_US
dc.identifier.citationAng, Wee Han, William Wesley Brown, and Stephen J. Lippard. “Preparation of Mammalian Expression Vectors Incorporating Site-Specifically Platinated-DNA Lesions.” Bioconjugate Chemistry 20, no. 5 (May 20, 2009): 1058-1063.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorAng, Wee Hanen_US
dc.contributor.mitauthorBrown, William Wesleyen_US
dc.contributor.mitauthorLippard, Stephen J.en_US
dc.relation.journalBioconjugate Chemistryen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsAng, Wee Han; Brown, William Wesley; Lippard, Stephen J.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2693-4982
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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