Cullinane C, Wickham G, McFadyen W D, Denny W A, Palmer B D, Phillips D R
Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
Nucleic Acids Res. 1993 Feb 11;21(3):393-400. doi: 10.1093/nar/21.3.393.
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.
双向转录足迹法已被用于探测顺铂对DNA的铂化作用，并研究（a）通过乙基或丙基使非反应性氨基环化，以及（b）进一步添加通过苯乙基或苯戊基连接的侧链嵌入剂对这些相互作用的调节。在模板链上所有5'-GG和5'-AG序列处，所有衍生物均检测到链内交联，但当这些位点位于非模板链上时，并未导致转录阻断。氨基环化几乎没有影响，但进一步添加嵌入剂会产生三种反应：被阻断转录本增加一个和三个核苷酸的时间依赖性增加；铂化作用序列选择性的降低；对于这些通过连接在顺铂氨基部分的侧链嵌入剂的衍生物，表观链间交联减少。
