The major adduct of the antitumor drug cis-diamminedichloroplatinum(II) with DNA bends the duplex by approximately equal to 40 degrees toward the major groove.
The major adduct of the antitumor drug cis-diamminedichloroplatinum(II) with DNA bends the duplex by approximately equal to 40 degrees toward the major groove.
复制标题
抗肿瘤药物顺式二氯二氨铂 (II) 与 DNA 的主要加合物使双链体向主沟弯曲约 40 度。
DOI：
10.1073/pnas.85.12.4158
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发表时间：
1988
影响因子：
11.1
通讯作者：
Lippard,SJ
中科院分区：
文献类型：
--
作者：
Rice,JA;Crothers,DM;Pinto,AL;Lippard,SJ
我们使用凝胶电泳方法显示，DNA与顺式二氨二氯铂（II）的反应导致在相邻鸟苷核苷的N7原子之间的链内交联处的双螺旋中的大量（约等于40度）弯曲，所述鸟苷核苷与铂（II）络合物键合，损失两个氯离子。多聚体的22个碱基对（bp）的寡核苷酸铂在一个单一的网站表现出强烈的异常，在其电泳迁移率作为一个结果的连贯性增加的相位铂诱导的弯曲。铂化位点的序列重复增加到27 bp产生几乎正常迁移率的多聚体，因为弯曲是异相的。Pt诱导的弯曲相对于腺苷道弯曲的方向是从多聚体的电泳迁移率确定的，其中重复的铂化位点在相对于重复的腺苷道的各种相位处相互交叉。当顺式-[Pt（NH3）2[d（pGpG）]]（N7，N7）加合物与腺苷束的中心分开1.5个螺旋圈时，发生最佳弯曲。这种定相产生了一致的附加腺苷束弯曲朝向小沟在其中心和铂诱导的弯曲朝向大沟，其中铂位于。
We used gel electrophoresis methods to show that reaction of DNA with cis-diamminedichloroplatinum(II) results in a substantial (approximately equal to 40 degrees) bend in the double helix at the intrastrand crosslink between the N7 atoms of adjacent guanosine nucleosides, which bond to the platinum(II) complex with loss of two chloride ions. Multimers of a 22-base-pair (bp) oligonucleotide platinated at a single site show strong anomalies in their electrophoretic mobilities as a consequence of coherent addition of in-phase platinum-induced bends. Increase of the sequence repeat of the platinated site to 27 bp yields multimers of nearly normal mobility because the bends are out of phase. The direction of Pt-induced bends relative to adenosine-tract bends was determined from the electrophoretic mobility of multimers in which repeated platination sites are interdigitated at various phasings relative to repeated adenosine tracts. Optimum bending occurs when 1.5 helical turns separate the cis-[Pt(NH3)2[d(pGpG)]](N7,N7) adducts from the center of the adenosine tracts. This phasing produces coherent addition of adenosine tract bends toward the minor groove at their centers and Pt-induced bends toward the major groove, where the platinum is located.