Analysis of cooperativity and ion effects in the interaction of quinacrine with DNA
Analysis of cooperativity and ion effects in the interaction of quinacrine with DNA
复制标题
奎纳克林与 DNA 相互作用的协同性和离子效应分析
作者：
W. Wilson;I. Lopp
使用分光光度法和平衡透析技术在几种不同的离子强度下监测奎纳克林与小牛胸腺 DNA 的相互作用。假设每个碱基对都是潜在的结合位点，使用包含两种负协同效应的模型可以解释结合结果：（1）与填充的结合位点相邻的结合位点处的配体排斥和（2）相邻填充的结合位点处的配体-配体负协同作用。由该模型确定的观察到的平衡常数 (Kobs) 的对数随 log[Na+] 线性变化，正如聚电解质离子凝聚理论所预测的那样。当对数 Kobs 图与嵌入构象变化中 DNA 释放的钠相关时，配体和 DNA 之间的预测离子对数量约为 2，正如对奎纳克林双标所预期的那样。尽管 Kobs 强烈依赖于离子强度，但在实验误差范围内，配体负协同参数 ω 与离子强度无关。这一发现也与离子凝聚理论相一致，该理论预测在此离子强度范围内，DNA 双螺旋上的凝聚抗衡离子数量相对恒定。因此，当药物与 DNA 复合时，即使溶剂的离子条件可能发生很大变化，也会经历相对恒定的离子环境。
The interaction of quinacrine with calf thymus DNA was monitored at several different ionic strengths using spectrophotometric and equilibrium dialysis techniques. The binding results can be explained, assuming each base pair is a potential binding site, using a model containing two negative cooperative effects: (1) ligand exclusion at binding sites adjacent to a filled binding site and (2) ligand–ligand negative cooperativity at adjacent filled binding sites. The logarithm of the observed equilibrium constant (Kobs) determined by this model varies linearily with log[Na+], as predicted by the ion condensation theory for polyelectrolytes. When the log Kobs plot is correlated for sodium release by DNA in the intercalation conformational change, the predicted number of ion pairs between the ligand and DNA is approximately two, as expected for the quinacrine dication. Even though Kobs depends strongly on ionic strength, the ligand negative cooperativity parameter ω was found to be indpendent of ionic strength within experimental error. This finding is also in agreement with the ion condensation theory, which predicts a relatively constant amount of condensed counterion on the DNA double helix over this ionic strength range. Drugs would, therefore, experience a relatively constant ionic environment when complexed to DNA even though the ionic conditions of the solvent could change considerably.