Energetics of DNA Intercalation Reactions
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- 作者：Jinsong Ren ; Terence C. Jenkins ; and Jonathan B. Chaires
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：July 25, 2000
- 年：2000
- 卷：39
- 期：29
- 页码：8439 - 8447
- 全文大小：365K
- 年卷期：v.39,no.29(July 25, 2000)
- ISSN：1520-4995
文摘
Isothermal titration calorimetry has been used to determine the binding enthalpy and heatcapacity change (
Cp) for a series of DNA intercalators, including ethidium, propidium, daunorubicin,and adriamycin. Temperature-dependent binding enthalpies were measured directly for the ligands, fromwhich Cp values of -140 to -160 cal mol-1 K-1 were calculated. Published van't Hoff plots werereanalyzed to obtain Cp values of -337 to -423 cal mol-1 K-1 for the binding of actinomycin D toseveral DNA oligonucleotide duplexes with defined sequences. Heat capacity changes for DNA intercalationwere found to correlate with the alterations in solvent-accessible surface area calculated from availablehigh-resolution structural data. Multiple linear regression was used to derive the relationship Cp = 0.382(±0.026)Anp - 0.121(±0.077)Ap cal mol-1 K-1, where Anp and Ap are the binding-induced changesin nonpolar and polar solvent-accessible surface areas (in square angstroms), respectively. The Cp termswere used to estimate the hydrophobic contribution to intercalative binding free energies, yielding valuesthat ranged from -11.2 (ethidium) to -30 kcal mol-1 (actinomycin D). An attempt was made to parsethe observed binding free energies of ethidium and propidium into five underlying contributions. Suchanalysis showed that the DNA binding behavior of these simple intercalators is driven almost equally byhydrophobic effects and van der Waals contacts within the intercalation site.
Cp) for a series of DNA intercalators, including ethidium, propidium, daunorubicin,and adriamycin. Temperature-dependent binding enthalpies were measured directly for the ligands, fromwhich Cp values of -140 to -160 cal mol-1 K-1 were calculated. Published van't Hoff plots werereanalyzed to obtain Cp values of -337 to -423 cal mol-1 K-1 for the binding of actinomycin D toseveral DNA oligonucleotide duplexes with defined sequences. Heat capacity changes for DNA intercalationwere found to correlate with the alterations in solvent-accessible surface area calculated from availablehigh-resolution structural data. Multiple linear regression was used to derive the relationship Cp = 0.382(±0.026)Anp - 0.121(±0.077)Ap cal mol-1 K-1, where Anp and Ap are the binding-induced changesin nonpolar and polar solvent-accessible surface areas (in square angstroms), respectively. The Cp termswere used to estimate the hydrophobic contribution to intercalative binding free energies, yielding valuesthat ranged from -11.2 (ethidium) to -30 kcal mol-1 (actinomycin D). An attempt was made to parsethe observed binding free energies of ethidium and propidium into five underlying contributions. Suchanalysis showed that the DNA binding behavior of these simple intercalators is driven almost equally byhydrophobic effects and van der Waals contacts within the intercalation site.