Circular dichroism study of the irreversibility of conformational changes induced by polyamine-linked dinuclear platinum compounds.
Circular dichroism study of the irreversibility of conformational changes induced by polyamine-linked dinuclear platinum compounds.
复制标题
DOI：
10.1016/s0162-0134(02)00398-7
复制
发表时间：
2002-07
影响因子：
3.9
通讯作者：
T. D. McGregor;W. Bousfield;Y. Qu;N. Farrell
中科院分区：
文献类型：
--
作者：
T. D. McGregor;W. Bousfield;Y. Qu;N. Farrell
本文研究了多核铂化合物诱导聚合物DNA中B→Z和B→A构象变化的可逆性。检查的化合物为：[{trans-PtCl（NH3）2}2{NH 2（CH 2）6 NH 2}]2+（BBR 3005）; [{trans-PtCl（NH3）2}2{μ-精胺-N1，N12}]4+（BBR 3535）; [{trans-PtCl（NH3）2}2{μ-精脒-N1，N8}]3+（BBR 3571）; [{trans-PtCl（NH3）2}2{μ-BOC-精脒}]2+（BBR 3537）;和[{trans-PtCl（NH3）2}2{μ-trans-Pt（NH3）2（H2N（CH2）6NH2）2}]4+（BBR 3464）。通过圆二色性评估构象变化，并通过随后的滴定与DNA嵌入剂溴化乙锭（EtBr）的转换的可逆性进行测试。还使用荧光猝灭来评估溴化乙锭嵌入由化合物诱导的A和/或Z-DNA中的能力。并与简单的六氨合钴阳离子[Co（NH 3）6]3+所产生的结果进行了比较。这些数据表明，虽然静电相互作用引起的构象变化被证实是可逆的，共价结合引起的A和Z构象的不可逆变化。这些变化的多核铂化合物的新的生物作用的相关性进行了讨论。
In this work, the reversibility of both the B→Z and B→A conformational change in polymer DNA induced by polynuclear platinum compounds was studied. The compounds examined were: [{trans-PtCl(NH3)2}2{NH2(CH2)6NH2}]2+(BBR3005); [{trans-PtCl(NH3)2}2{μ-spermine-N1,N12}]4+(BBR3535); [{trans-PtCl(NH3)2}2{μ-spermidine-N1,N8}]3+(BBR3571); [{trans-PtCl(NH3)2}2{μ-BOC-spermidine}]2+(BBR3537); and [{trans-PtCl(NH3)2}2{μ-trans-Pt(NH3)2(H2N(CH2)6NH2)2}]4+(BBR3464). The conformational changes were assessed by circular dichroism and the reversibility of the transitions was tested by subsequent titration with the DNA intercalator ethidium bromide (EtBr). Fluorescent quenching was also used to assess the ability of ethidium bromide to intercalate into A and/or Z-DNA induced by the compounds. The results were compared with those produced by the simple hexamminecobalt cation [Co(NH3)6]3+. The data suggest that while conformational changes induced by electrostatic interactions are confirmed to be reversible, covalent binding induces irreversible changes in both the A and Z conformation. The relevance of these changes to the novel biological action of polynuclear platinum compounds is discussed.