title: The use of bidirectional transcription footprinting to detect platinum-DNA crosslinks by acridine-tethered platinum diamine complexes and cisplatin.
abstract: Bidirectional transcription footprinting has been used to probe the platination of DNA by cisplatin, and to examine the modulation of these interactions by (a) cyclisation of the non-reactive amino group by either ethyl or propyl groups, and (b) the further addition of a pendant intercalator (9-amino acridine) linked by either phenylethyl or phenylpentyl groups. Intrastrand crosslinking was detected for all derivatives at all 5'-GG and 5'-AG sequences on the template strand, but the same sites did not result in transcriptional blockages when on the non-template strand. There was little effect of cyclysation of the amino groups, but the further addition of an intercalator resulted in three responses: a time-dependent increase of the blocked transcript by one and three nucleotides; a reduction of the sequence selectivity of platination; a decrease of apparent interstrand crosslinking for these derivatives with a pendant intercalator tethered to the amino moiety of cisplatin.
authors.affiliation: Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Cullinane
authors.forename: G
authors.initials: G
authors.lastname: Wickham
authors.forename: W D
authors.initials: WD
authors.lastname: McFadyen
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
authors.forename: B D
authors.initials: BD
authors.lastname: Palmer
authors.forename: D R
authors.initials: DR
authors.lastname: Phillips
mesh_terms: D000166:Acridines / Q000737:chemistry; D001483:Base Sequence; D002945:Cisplatin / Q000031:analogs & derivatives / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010984:Platinum / Q000032:analysis / Q000737:chemistry*; D014158:Transcription, Genetic
chemical_list: D000166:Acridines; D003432:Cross-Linking Reagents; D010984:Platinum; D004247:DNA; D002945:Cisplatin