Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes.
Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes.
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道诺霉素-DNA 相互作用的热力学表征：一系列 DNA 宿主双链体的完整结合谱的比较。
DOI：
10.1021/bi00070a014
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Breslauer,KJ
中科院分区：
文献类型：
--
作者：
Remeta,DP;Mudd,CP;Berger,RL;Breslauer,KJ
1993年3月10日收到的修订手稿摘要：使用光谱和量热技术的组合，我们已经确定了柔红霉素与一系列10个聚合DNA双链络合的完整热力学结合谱(0，AH0和AS0)。我们发现所得到的药物结合数据对主体双链体的碱基组成和序列很敏感，结合自由能在25℃时为结合药物的-7.5~-10.8千卡/摩尔，结合热焓为+4.11~-10.76千卡/摩尔，自由能项中较小的范围反映了大的热焓-熵补偿的影响。我们观察到，表现出最高柔红霉素结合亲和力的三个合成双链都含有GC(或IC)碱基对作为交替的嘌呤/嘧啶序列基序的一部分，这些高结合亲和力在25℃时被强烈的热能驱动。通过对柔红霉素与特定的宿主双链体结合图谱的具体比较，得到以下观察结果：(1)大沟槽甲基的存在或不存在并不改变柔红霉素的结合热力学。(2)小沟槽氨基的存在或不存在确实改变了柔红霉素的结合热力学。(3)碱基组成不同但小沟槽官能度相同的双链体表现出相似的柔红霉素结合热力学。(4)由AT或AU碱基对组成的均多核双链体，而不是GC碱基对，在它们的柔红霉素结合图谱中表现出较大的焓-熵补偿。我们从现有的结构数据出发，根据柔红霉素与DNA的相互作用，对热力学数据的这些和其他特征提出了解释。
Revised Manuscript Received March 10, 1993 abstract: Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (0, AH0, and AS0) for the complexation of daunomycin to a series of 10 polymeric DNA duplexes. We find the resulting drug binding data to be sensitive to the base composition and sequence of the host duplex, with the binding free energies ranging from-7.5 to-10.8 kcal/mol of bound drug and the binding enthalpies ranging from+ 4.11 to-10.76 kcal/molof bound drug at 25 C. The smaller range in the free energy term reflects the impact of large enthalpy-entropy compensations. We observe that the three synthetic duplexes which exhibit the highest daunomycin binding affinities all contain GC (or IC) base pairs as part of alternating purine/pyrimidine sequence motifs, with these high binding affinities being strongly enthalpy driven at 25 C. Specific comparisons between the binding profiles for daunomycin complexation with select pairs of host duplexes lead to the following observations:(1) The presence or absence of a major-groove methyl group does not alter daunomycin binding thermodynamics.(2) The presence or absence of a minor-groove amino group does alter daunomycin binding thermodynamics.(3) Duplexes with different base compositions but identical minor-groove functionality exhibit similar daunomycin binding thermodynamics.(4) Homopolytneric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy-entropy compensations intheir daunomycin binding profiles. We propose interpretations of these and other features of our thermodynamic data in terms of specific daunomycin-DNA interactions deduced from available structural data.