Equilibrium binding of carcinogens and antitumor antibiotics to DNA: site selectivity, cooperativity, allosterism
Equilibrium binding of carcinogens and antitumor antibiotics to DNA: site selectivity, cooperativity, allosterism
复制标题
致癌物和抗肿瘤抗生素与 DNA 的平衡结合：位点选择性、协同性、变构作用
DOI：
10.1093/nar/9.13.3175
复制
发表时间：
1981
影响因子：
14.9
通讯作者：
T. Krugh
中科院分区：
文献类型：
--
作者：
S. Winkle;T. Krugh
采用相分配技术研究了致癌物N-羟基-N-乙酰基-2-氨基-芴（HAAF）和4-硝基喹啉-1-氧化物（NQO）与phi X174 RF DNA的平衡结合。两种分子以合作的方式结合，只有少数致癌分子与每个phi X174 RF DNA分子结合。HAAF和NQO的结合数据符合一个模型，其中两种致癌物聚集在少量的位点上--HAAF有4个位点，NQO有12个位点。还采用相分配技术研究了放线菌素D与小牛胸腺DNA和poly（dG-dC）的结合。聚（dG-dC）在比以前报道的低得多的r值。这些数据显示出驼峰Scatchard图，这表明协同结合; Scatchard图的整体形状与DNA结构中药物诱导的变构转换模型一致。放线菌素D与小牛胸腺DNA结合的协同性随着氯化钠浓度的降低而增加，这表明DNA柔性在变构结合中的作用。
The equilibrium binding of the carcinogens N-hydroxy-N-acetyl-2-amino-fluorene (HAAF) and 4-nitroquinoline-1-oxide (NQO) to phi X174RF DNA have been studied by phase partition techniques. Both molecules bind in a cooperative manner with only a few carcinogen molecules binding to each phi X174RF DNA molecule. The binding data for both HAAF and NQO fit a model in which two carcinogens cluster into a small number of sites--four sites for HAAF and twelve sites for NQO. Phase partition techniques were also used to study the binding of actinomycin D to both calf thymus DNA and poly (dG-dC) . poly (dG-dC) at much lower r values than had been previously reported. These data exhibit humped Scatchard plots which are indicative of cooperative binding; the overall shape of the Scatchard plots are consistent with a model for drug induced allosteric transitions in the DNA structure. The cooperativity in the actinomycin D binding to calf thymus DNA increases with decreasing sodium chloride concentration, suggesting a role for DNA flexibility in allosteric binding.