Structure and dynamics of distamycin A with d(CGCAAATTGGC):d(GCCAATTTGCG) at low drug:DNA ratios.
Structure and dynamics of distamycin A with d(CGCAAATTGGC):d(GCCAATTTGCG) at low drug:DNA ratios.
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低药物:DNA 比率下偏端霉素 A 与 d(CGCAATTGGC):d(GCCAATTTGCG) 的结构和动力学。
DOI：
10.1080/07391102.1990.10507791
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发表时间：
1990
影响因子：
4.4
通讯作者：
Wemmer,DE
中科院分区：
文献类型：
--
作者：
Pelton,JG;Wemmer,DE
二维NMR已用于研究偏端霉素A与d（CGCAAA-TTGGC）：d（GCCAATTTGCG）在低和中等药物：DNA比率（<2.0）下的相互作用。通过核Overhauser效应光谱法鉴定药物-DNA接触，所述核Overhauser效应光谱法还用于监测药物在不同结合位点之间的交换。在低药物浓度下：DNA比率（0.5），偏端霉素A在5个中心A-T碱基对内以两个方向结合，并优先（2.2：1）与指向富含A链5′侧的甲酰基末端结合。对应于优选结合方向的药物-DNA接触的模式与药物在相邻AAAT和AATT结合位点之间以在NMR时间尺度上快的速率滑动一致。类似地，与不太有利的取向相关的NOE的模式与相邻AATT和ATTT位点之间的药物滑动一致，再次在快速交换中。在35°C下，药物从主要和次要结合方向的解离速率分别为2.4 =1.5和3.3 = 1.5 s-1。在中间药物：DNA比率（1.3）下，观察到两种单药物和两种药物复合物的两个位点之间的药物交换。两种药物从2：1复合物的解离速率测量为1.0 =0.5 s-1（35°C）。
Two-dimensional NMR has been used to study the interaction of distamycin A with d(CGCAAA- TTGGC):d(GCCAATTTGCG) at low and intermediate drug: DNA ratios (<2.0). Drug-DNA contacts were identified by nuclear Overhauser effect spectroscopy, which also served to monitor exchange of the drug between different binding sites. At low drug: DNA ratios (0.5), distamycin A binds in two orientations within the five central A-T base pairs and has a preference (2.2:1) for binding with the formyl end directed toward the 5′ side of the A-rich strand. The pattern of drug-DNA contacts corresponding to the preferred binding orientation are consistent with the drug sliding between adjacent AAAT and AATT binding sites at a rate that is fast on the NMR time scale. Similarly, the pattern of NOEs associated with the less favored orientation are consistent with the drug sliding between adjacent AATT and ATTT sites, again in fast exchange. Off-rates for the drug from the major and minor binding orientations were measured to be 2.4 =1.5 and 3.3 = 1.5 s−1respectively, at 35°C. At intermediate drug: DNA ratios (1.3) exchange of the drug between the two one-drug and the two sites of a two-drug complex is observed. Off-rates for both drugs from the 2:1 complex were measured to be 1.0 =0.5 s−1(35°C).