Nucleotide-specific cleavage and minor-groove interaction of DNA with esperamicin antitumor antibiotics.
Nucleotide-specific cleavage and minor-groove interaction of DNA with esperamicin antitumor antibiotics.
复制标题
DNA 与埃斯帕霉素抗肿瘤抗生素的核苷酸特异性切割和小沟相互作用。
DOI：
10.1073/pnas.86.20.7672
复制
发表时间：
1989
影响因子：
11.1
通讯作者：
T. Doyle
中科院分区：
文献类型：
--
作者：
Y. Sugiura;Y. Uesawa;Y. Takahashi;J. Kuwahara;J. Golik;T. Doyle
在硫醇化合物存在下，埃斯波霉素对DNA的切割大大加速。氧和活性氧自由基清除剂对埃培霉素引起的DNA链断裂没有显著影响。埃斯波霉素的优先切割位点在胸苷酸残基处，并且被攻击的碱基的频率（T大于C大于A大于G）不同于卡奇霉素（C远大于T大于A = G）、新制癌素（T大于A大于C大于G）或博来霉素（C大于T大于A大于G）。埃斯帕霉素优先攻击寡嘧啶序列如5 '-CTC-3'、5 '-TTC-3'和5 '-TTT-3'中的T和C碱基。与博来霉素切割的优选位点5 '-GT-3'和5 '-GC-3'相反，埃斯培拉霉素介导的DNA降解的优选位点是5 '-TG-3'和5 '-CG-3'序列。用netropsin和偏端霉素A预处理DNA显著影响了esperamicin的核苷酸特异性切割模式，表明esperamicin的相互作用通过B-DNA的小沟发生。这进一步得到了DNA相对链上3'侧的不对称切割模式的支持。岩藻糖邻氨基苯甲酸酯部分和三糖侧链的esperamicin在DNA结合和碱基识别的作用进行了讨论。
The cleavage of DNA by esperamicin is greatly accelerated in the presence of thiol compounds. Oxygen and active oxygen-radical scavengers have no significant influence upon DNA strand breakage by esperamicin. The preferential cutting sites of esperamicin are at thymidylate residues, and the frequency of bases attacked (T greater than C greater than A greater than G) is different from that of calicheamicin (C much greater than T greater than A = G), neocarzinostatin (T greater than A greater than C greater than G), or bleomycin (C greater than T greater than A greater than G). Esperamicin preferentially attacks at T and C bases in oligopyrimidine sequences such as 5'-CTC-3', 5'-TTC-3', and 5'-TTT-3'. In contrast to the preferred sites of cleavage by bleomycin, 5'-GT-3' and 5'-GC-3', the preferred sites of esperamicin-mediated DNA degradation are 5'-TG-3' and 5'-CG-3' sequences. The nucleotide-specific cleavage mode of esperamicin is significantly affected by pretreatment of DNA with netropsin and distamycin A, suggesting that interaction of esperamicin occurs through the minor groove of B-DNA. This is further supported by the asymmetric cleavage pattern to the 3' side on the opposite strand of the DNA. The roles of the fucose-anthranilate moiety and the trisaccharide side chain of esperamicin in DNA binding and base recognition are discussed.