dc.contributor.author | Ruhayel, Rasha A | |
dc.contributor.author | Moniodis, Joseph J | |
dc.contributor.author | Yang, Xiaohong | |
dc.contributor.author | Kasparkova, Jana | |
dc.contributor.author | Brabec, Viktor | |
dc.contributor.author | Berners-Price, Susan J | |
dc.contributor.author | Farrell, Nicholas P | |
dc.date.accessioned | 2018-02-13T03:25:26Z | |
dc.date.available | 2018-02-13T03:25:26Z | |
dc.date.issued | 2009 | |
dc.date.modified | 2010-08-13T07:22:43Z | |
dc.identifier.issn | 0947-6539 | |
dc.identifier.doi | 10.1002/chem.200900958 | |
dc.identifier.uri | http://hdl.handle.net/10072/30179 | |
dc.description.abstract | Reported 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Wiley-VCH Verlag GmbH & Co. KGaA | |
dc.publisher.place | Germany | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 9365 | |
dc.relation.ispartofpageto | 9374 | |
dc.relation.ispartofissue | 37 | |
dc.relation.ispartofjournal | Chemistry - A European Journal | |
dc.relation.ispartofvolume | 15 | |
dc.relation.uri | http://purl.org/au-research/grants/ARC/DP0662817 | |
dc.relation.grantID | DP0662817 | |
dc.relation.funders | ARC | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Chemical sciences | |
dc.subject.fieldofresearch | Bioinorganic chemistry | |
dc.subject.fieldofresearchcode | 34 | |
dc.subject.fieldofresearchcode | 340201 | |
dc.title | Factors affecting DNA-DNA interstrand cross-links in the antiparallel 3'-3' sense: a comparison with the 5'-5' directional isomer | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2009 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Berners-Price, Sue J. | |