Prakash A S, Moore A G, Murray V, Matias C, McFadyen W D, Wickham G
Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
Chem Biol Interact. 1995 Mar 30;95(1-2):17-28. doi: 10.1016/0009-2797(94)03341-2.
The sequence selectivity of DNA alkylation by the recently isolated pluramycin antitumour antibiotic DC92-B has been investigated using two methods: a piperidine-induced strand-breaking procedure and a Taq DNA polymerase/linear amplification method. These techniques reveal that guanines are the most reactive sites for alkylation and that the level of adduct formation at these sites is clearly sequence dependent. The highest levels of alkylation occurred at isolated guanines located in 5'-CGT sequences and also at the 5'-G in some 5'-CGG sequences. Isolated guanines in 5'-TGT sequences were also quite reactive. We have also re-examined, in parallel, the sequence selectivity of binding of the structurally-related compound hedamycin: the first known example of a bis(epoxide)-containing, DNA-alkylating pluramycin. Our studies included a more extensive sequence analysis of hedamycin binding than that previously reported and we are able, therefore, to define more precisely the sequence preference. Despite significant differences in the stereochemistry and substitution of their bis(epoxide) sidechains, hedamycin and DC92-B exhibited very similar sequence selectivities in our assays.
利用两种方法研究了最近分离出的多色霉素抗肿瘤抗生素DC92 - B对DNA的烷基化序列选择性：哌啶诱导的链断裂程序和Taq DNA聚合酶/线性扩增方法。这些技术表明，鸟嘌呤是最易发生烷基化的位点，并且这些位点处加合物的形成水平明显依赖于序列。烷基化水平最高的情况发生在位于5'-CGT序列中的孤立鸟嘌呤处，以及一些5'-CGG序列中的5'-G处。5'-TGT序列中的孤立鸟嘌呤也具有较高的反应活性。我们还同时重新研究了结构相关化合物赫达霉素的结合序列选择性：赫达霉素是第一个已知的含双（环氧化物）的DNA烷基化多色霉素。我们的研究包括对赫达霉素结合进行比之前报道更广泛的序列分析，因此我们能够更精确地确定序列偏好。尽管它们双（环氧化物）侧链的立体化学和取代存在显著差异，但在我们的测定中，赫达霉素和DC92 - B表现出非常相似的序列选择性。
