Show simple item record

dc.contributor.authorRuhayel, Rasha A
dc.contributor.authorMoniodis, Joseph J
dc.contributor.authorYang, Xiaohong
dc.contributor.authorKasparkova, Jana
dc.contributor.authorBrabec, Viktor
dc.contributor.authorBerners-Price, Susan J
dc.contributor.authorFarrell, Nicholas P
dc.date.accessioned2018-02-13T03:25:26Z
dc.date.available2018-02-13T03:25:26Z
dc.date.issued2009
dc.date.modified2010-08-13T07:22:43Z
dc.identifier.issn0947-6539
dc.identifier.doi10.1002/chem.200900958
dc.identifier.urihttp://hdl.handle.net/10072/30179
dc.description.abstractReported herein is a study of the unusual 3′–3′ 1,4-GG interstrand cross-link (IXL) formation in duplex DNA by a series of polynuclear platinum anticancer complexes. To examine the effect of possible preassociation through charge and hydrogen-bonding effects the closely related compounds [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (BBR3464, 1), [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]2+ (BBR3005, 2), [{trans-PtCl(NH3)2}2(μ-H2N(CH2)3NH2(CH2)4)]3+ (BBR3571, 3) and [{trans-PtCl(NH3)2}2{μ-H2N(CH2)3-N(COCF3)(CH2)4}]2+ (BBR3571-COCF3, 4) were studied. Two different molecular biology approaches were used to investigate the effect of DNA template upon IXL formation in synthetic 20-base-pair duplexes. In the “hybridisation directed” method the monofunctionally adducted top strands were hybridised with their complementary 5′-end labelled strands; after 24 h the efficiency of interstrand cross-linking in the 5′–5′ direction was slightly higher than in the 3′–3′ direction. The second method involved “postsynthetic modification” of the intact duplex; significantly less cross-linking was observed, but again a slight preference for the 5′–5′ duplex was present. 2D [1H, 15N] HSQC NMR spectroscopy studies of the reaction of [15N]-1 with the sequence 5′-d{TATACATGTATA}2 allowed direct comparison of the stepwise formation of the 3′–3′ IXL with the previously studied 5′–5′ IXL on the analogous sequence 5′-d(ATATGTACATAT)2. Whereas the preassociation and aquation steps were similar, differences were evident at the monofunctional binding step. The reaction did not yield a single distinct 3′–3′ 1,4-GG IXL, but numerous cross-linked adducts formed. Similar results were found for the reaction with the dinuclear [15N]-2. Molecular dynamics simulations for the 3′–3′ IXLs formed by both 1 and 2 showed a highly distorted structure with evident fraying of the end base pairs and considerable widening of the minor groove.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley-VCH Verlag GmbH & Co. KGaA
dc.publisher.placeGermany
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom9365
dc.relation.ispartofpageto9374
dc.relation.ispartofissue37
dc.relation.ispartofjournalChemistry - A European Journal
dc.relation.ispartofvolume15
dc.relation.urihttp://purl.org/au-research/grants/ARC/DP0662817
dc.relation.grantIDDP0662817
dc.relation.fundersARC
dc.rights.retentionY
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchBioinorganic chemistry
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode340201
dc.titleFactors affecting DNA-DNA interstrand cross-links in the antiparallel 3'-3' sense: a comparison with the 5'-5' directional isomer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2009
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