Thermodynamic Characterization of Daunomycin-DNA Interactions: Comparison of Complete Binding Profiles for a Series of DNA Host Duplexes

David P. Remeta, Kenneth J. Breslauer, Courtney P. Mudd, Robert L. Berger

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (ΔG°, ΔH°, and ΔS°) 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/mol of 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) Homopolymeric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy–entropy compensations in their 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.

Original languageEnglish (US)
Pages (from-to)5064-5073
Number of pages10
JournalBiochemistry
Volume32
Issue number19
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry

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