Thermodynamic characterization of daunomycin-DNA interactions: microcalorimetric measurements of daunomycin-DNA binding enthalpies.
Thermodynamic characterization of daunomycin-DNA interactions: microcalorimetric measurements of daunomycin-DNA binding enthalpies.
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道诺霉素-DNA 相互作用的热力学表征：道诺霉素-DNA 结合焓的微量热测量。
DOI：
10.1021/bi00104a032
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发表时间：
1991
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
修订稿于 1991 年 7 月 22 日收到摘要：我们报告了首次直接测定单体道诺霉素与一系列 10 个聚合 DNA 双链体络合的结合焓。这些测量是通过使用最近开发的停流微热量计来完成的，该热量计能够检测微焦耳级别的反应热。这种增强的灵敏度使我们能够测量单体药物浓度（例如 10-20 µ）下的道诺霉素-DNA 结合焓，从而无需像之前批量量热研究中所要求的那样校正道诺霉素自缔合[Remeta, D. P., Marky, LA, & Breslauer, K. J.(1984) 匹兹堡会议和分析化学博览会摘要应用光谱学，838a； Breslauer, K. J.、Remeta, D. P.、Chou, WY、Ferrante, R.、Curry, J.、Zaunczkowski, D.、Snyder, J. G. 和 Marky, LA (1987) Proc。国家。阿卡德。科学。美国 84, 8922-8926]。我们校正了已发表的在较高药物浓度（例如，0.5-1.0 M）下通过批量量热法测量的道诺霉素-DNA 结合焓，以了解与结合诱导的药物聚集体破坏相关的焓贡献。必要的校正项是通过对柔红霉素溶液的温度依赖性 NMR 测量进行 van’t Hoff 分析而获得的。我们发现从这些校正的批量量热数据得出的净结合焓与通过停流微量热法直接测量的相应结合焓之间存在显着的一致性。停流仪器灵敏度的提高也使我们能够评估药物结合密度对道诺霉素-DNA 结合焓的影响。该评估是通过对七种不同的药物与磷酸盐比率 (/·) 进行停流量热测量来完成的。对于所研究的 10 个 DNA 宿主双链体中的大多数，我们发现道诺霉素结合焓表现出较小但显着的 r 依赖性。停流仪器的灵敏度还使我们能够检测到几种不含药物的显着稀释焓。
Revised Manuscript Received July 22, 1991 abstract: We report the first direct determination of binding enthalpies for the complexation of monomeric daunomycin with a series of 10 polymeric DNA duplexes. These measurements were accomplished by using a recently developed stopped-fiow microcalorimeter capable of detecting reaction heats on the microjoule level. This enhanced sensitivity allowed us to measure daunomycin-DNA binding enthalpies at monomeric drug concentrations (eg, 10-20 ĩ), thereby precluding the need to correct for daunomycin self-association, as hasbeen required in previous batch calorimetric studies [Remeta, D. P., Marky, LA, & Breslauer, K. J.(1984) Abstracts of Pittsburgh Conference andExposition on Analytical Chemistry and Applied Spectroscopy, 838a; Breslauer, K. J., Remeta, D. P., Chou, WY, Ferrante, R., Curry, J., Zaunczkowski, D., Snyder, J. G., & Marky, LA (1987) Proc. Natl. Acad. Sci. USA 84, 8922-8926]. We correct the published daunomycin-DNA bindingenthalpies measured by batch calorimetry at higher drug concentrations (eg, 0.5-1.0 M) for the enthalpycontribution associated with the binding-induced disruption of drug aggregates. The requisite correction term was obtained from a van’t Hoff analysis of temperature-dependent NMR measurements on daunomycin solutions. We find remarkable agreement between the net binding enthalpies derived from these corrected batch calorimetric data and the corresponding binding enthalpies measured directly by stopped-fiow microcalorimetry. The enhanced sensitivity of the stopped-fiow instrument also allowed us to evaluate the influence of drug binding density on the daunomycin-DNA binding enthalpies. This assessment was accomplished by conducting stopped-fiow calorimetric measurements over a range of seven different drug-to-phosphate ratios (/·). For most of the 10 DNA host duplexes studied, we find that the daunomycin binding enthalpies exhibit small but significant r dependencies. The sensitivity of the stopped-fiow instrument also enabled us to detect significant dilution enthalpies for several of the drug-free
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DOI：
10.1073/pnas.86.11.3968
发表时间：
1989
影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.84.24.8922
发表时间：
1987-12-01
影响因子：
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作者：
BRESLAUER, KJ;REMETA, DP;MARKY, LA
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