Fox K R, Davies H, Adams G R, Portugal J, Waring M J
Department of Pharmacology, University of Cambridge, UK.
Nucleic Acids Res. 1988 Mar 25;16(6):2489-507. doi: 10.1093/nar/16.6.2489.
We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.
我们研究了抗肿瘤抗生素鲁佐肽与五个碱基组成不同的DNA片段的结合情况。该药物与DNA形成紧密的、可能是共价的复合物，导致其在非变性聚丙烯酰胺凝胶上的迁移率降低，并且条带出现一些拖尾现象，这与DNA双链的分子内交联一致。DNA酶I和微球菌核酸酶足迹实验表明，该药物与含有交替A和T残基的区域结合最佳，尽管没有出现一致的二核苷酸或三核苷酸序列。并不排除与其他位点的结合，并且在适度的配体浓度下，DNA几乎完全受到保护而免受酶的攻击。在富含AT和GC的区域均观察到配体诱导的DNA酶I切割增强。鲁佐肽结合的序列选择性和特征与相关结构的双功能嵌入剂棘霉素的序列选择性和特征有很大不同。
