Show simple item record

dc.contributor.authorBernersPrice, SJ
dc.contributor.authorBarnham, KJ
dc.contributor.authorFrey, U
dc.contributor.authorSadler, PJ
dc.date.accessioned2017-09-22T01:16:04Z
dc.date.available2017-09-22T01:16:04Z
dc.date.issued1996
dc.identifier.issn0947-6539
dc.identifier.doi10.1002/chem.19960021016
dc.identifier.urihttp://hdl.handle.net/10072/120811
dc.description.abstractWe report the first direct comparison of the kinetics of platination of defined single- and double-stranded DNA with the anticancer drug cisplatin. The courses of the reactions of the 14-mer duplex d(A-T-A-C-A-T-G-G-T-A-C-A-T-A)·d(T-A-T-G-T-A-C-C-A-T-G-T-A-T) with [15N]cisplatin and cis-[PtCl(H2O)-(15NH3)2]+ and of each of the single strands with [15N]cisplatin have been studied at 298 K, pH 6, by [1H, 15N] NMR spectroscopy. As expected the reactions of cisplatin proceed via cis-[PtCl(H2O)(NH3)2]+, and lead to two monofunctional adducts on the duplex and two on the GG single strand. In both the GG single strand and the duplex, one of the two G's is platinated faster than the other (by a factor of ca. 4). Remarkably, ring closure on the duplex to form the GG chelate occurs about an order of magnitude faster for one monofunctional adduct than for the other. The latter monofunctional adduct has distinctive 1H and 15N NMR chemical shifts for Pt-NH3, and is very long-lived (persists for >5 d). The Pt-Cl bond in this monofunctional adduct is protected from hydrolysis by the duplex. In contrast, the two monofunctional adducts on the GG single strand undergo ring closure at about the same rate. Equilibria between kinked and distorted forms of the GG platinated duplex, the platination of G's on the complementary strand, and the potential biological significance of long-lived monofunctional adducts of platinum drugs with DNA are discussed.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley - VCH
dc.publisher.placeGermany
dc.relation.ispartofpagefrom1283
dc.relation.ispartofpageto1291
dc.relation.ispartofjournalChemistry: a European Journal
dc.relation.ispartofvolume2 10
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchAnalytical chemistry not elsewhere classified
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode340199
dc.titleKinetic Analysis of the Stepwise Platination of Single- and Double-stranded GG Olignucleotides with Cisplatin and Cis-[PtCl(h2O)(NH3)2]
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.hasfulltextNo Full Text
gro.griffith.authorBerners-Price, Sue J.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record