Calorimetric and spectroscopic investigation of drug-DNA interactions: II. Dipyrandlam binding to poly d(AT)

Luis A. Marky, James G. Snyder, Kenneth J. Breslauer

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

We report the first calorimetric investigation of steroid diamine binding to a DNA duplex. Absorption spectroscopy, batch calorimetry, and differential scanning calorlmetry (DSC) have been used to detect, monitor, and therraodynamically characterize the binding of the steroid diamine, dipyrandium, to poly d(AT). The following theraodynamic data for the binding in 16 mM Na+ at 25°C have been obtained: δG° - -6.5 kcal/nol, δH° = +4.2 kcal/mol, and δS = +36 e.u. We interpret the endothermic binding enthalpy in terms of steroid-induced conformational changes in the duplex (e.g. "kinking"). The large positive entropy is interpreted in terms of binding-induced release of bound water and condensed sodium ions. The salt-dependence of the binding constant is interpreted in terms of dipyrandium site-binding involving only one of the two charged ends of the steroid. The optical and DSC curves for the unsaturated steroid-poly d(AT) complexes exhibit biphasic behavior. A comparison of the van't Hoff and the calorimetric transition enthalpies reveals that steroid binding reduces the cooperativlty of the transition.

Original languageEnglish (US)
Pages (from-to)5701-5715
Number of pages15
JournalNucleic acids research
Volume11
Issue number16
DOIs
StatePublished - Aug 25 1983

ASJC Scopus subject areas

  • Genetics

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