Sequence preferences of DNA interstrand cross-linking agents: dG-to-dG cross-linking at 5'-CG by structurally simplified analogues of mitomycin C.
Sequence preferences of DNA interstrand cross-linking agents: dG-to-dG cross-linking at 5'-CG by structurally simplified analogues of mitomycin C.
复制标题
DNA 链间交联剂的序列偏好：通过结构简化的丝裂霉素 C 类似物在 5-CG 处进行 dG 到 dG 交联。
DOI：
10.1021/bi00491a017
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Hopkins,PB
中科院分区：
文献类型：
--
作者：
Weidner,MF;Sigurdsson,ST;Hopkins,PB
华盛顿大学化学系，西雅图，华盛顿98195，1990年4月4日接收; 1990年7月3日接收的修订版摘要：DNA链间交联剂二乙酸脱氢逆转录酶（DHRA）、2，3-双用合成的DNA双链体片段和聚丙烯酰胺凝胶电泳（PAGE）研究了（乙酰氧基甲基）-l-甲基吡咯（BAMP）、脱氢野百合碱和脱氢倒甲草碱。这些药物具有与丝裂霉素C（MC）的还原活化的氮丙啶缩氮素相同的结构特征。与MC一样，它们优先交联含有双链体序列5 '-CG的DNA双链体。对于DHRA和BAMP链间交联的DNA双链体，铁（II）-EDTA断裂反应的PAGE分析显示链间交联是脱氧鸟苷到脱氧鸟苷（dG到dG），再次类似于MC引起的DNA交联。与MC不同，DHRA可显示dG至dG交联5 '-GC序列。此外，对于BAMP，侧翼序列对5 '-CG处的链间交联效率的影响降低，5'-TCGA和5 '-GCGC同样有效地交联。讨论了所有试剂共同的5 '-CG序列识别的可能起源。提出了一个模型，其中单加合物转化为交联的过渡态更接近于基态DNA在5 '-CG序列。
Department of Chemistry, University of Washington, Seattle, Washington 98195 Received April 4, 1990; Revised Manuscript Received July 3, 1990 abstract: The nucleotide sequence preferences of the DNA interstrand cross-linking agents dehydroretronecine diacetate (DHRA), 2, 3-bis (acetoxymethyl)-l-methylpyrrole (BAMP), dehydromonocrotaline, and dehydroretrorsine were studied by using synthetic DNA duplex fragments and polyacrylamide gel electrophoresis (PAGE). These agents have structural features in common with the reductively activated aziridinomitosene of mitomycinC (MC). Like MC, they preferentially cross-linked DNA duplexes containing the duplex sequence 5'-CG. For DHRA and BAMP interstrand cross-linked DNA duplexes, PAGE analysis of iron (II)-EDTA fragmentation reactionsrevealed the interstrand cross-links to be deoxyguanosine to deoxyguanosine (dG-to-dG), again analogous to DNA cross-links caused by MC. Unlike MC, DHRA could be shown to dG-to-dG cross-link a 5'-GC sequence. Furthermore, the impact of flanking sequence on the efficiency of interstrand cross-linking at 5'-CG was reduced for BAMP, with 5'-TCGA and 5'-GCGC being equally efficiently cross-linked. Possible origins of the 5'-CG sequence recognition common to all of the agents are discussed. A model is presented in which the transition state for the conversion of monoadducts to cross-links more closely resembles ground-state DNA at 5'-CG sequences.