Bailly C, Crow S, Minnock A, Waring M J
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Lille, France.
Nucleosides Nucleotides Nucleic Acids. 2000 Aug;19(8):1337-53. doi: 10.1080/15257770008033056.
The luzopeptin antibiotics contain a cyclic decadepsipeptide to which are attached two quinoline chromophores that bisintercalate into DNA. Although they bind DNA less tightly than the structurally related quinoxaline antibiotics echinomycin and triostin A, the molecular basis of their interaction remains unclear. We have used the PCR in conjunction with novel nucleotides to create specifically modified DNA for footprinting experiments. In order to study the influence that removal, addition or relocation of the guanine 2-amino group, which normally identifies G.C base pairs from the minor groove, has on the interaction of luzopeptin antibiotics with DNA. The presence of a purine 2-amino group is not strictly required for binding of luzopeptin to DNA, but the exact location of this group can alter the position of preferred drug binding sites. It is, however, not the sole determinant of nucleotide sequence recognition in luzopeptin-DNA interaction. Nor can the selectivity of luzopeptin be attributed to the quinoline chromophores, suggesting that an analogue mode of DNA recognition may be operative. This is in contrast to the digital readout that seems to predominate with the quinoxaline antibiotics.
鲁佐肽抗生素含有一个环状十肽缩酚酸肽，其上连接有两个喹啉发色团，这两个发色团会双插入到DNA中。尽管它们与DNA的结合不如结构相关的喹喔啉抗生素棘霉素和曲奥菌素A紧密，但其相互作用的分子基础仍不清楚。我们利用聚合酶链式反应（PCR）结合新型核苷酸来制备用于足迹实验的特异性修饰DNA。为了研究去除、添加或重新定位通常从小沟中识别G.C碱基对的鸟嘌呤2-氨基对鲁佐肽抗生素与DNA相互作用的影响。鲁佐肽与DNA结合并不严格需要嘌呤2-氨基的存在，但该基团的确切位置可以改变优选药物结合位点的位置。然而，它不是鲁佐肽-DNA相互作用中核苷酸序列识别的唯一决定因素。鲁佐肽的选择性也不能归因于喹啉发色团这表明可能存在一种类似的DNA识别模式。这与喹喔啉抗生素似乎占主导的数字读出方式形成对比。
