Abstract
Double-helical calf thymus DNA and poly dG:dC produced marked changes in the absorption spectrum of quinine. Single-stranded DNA, poly dA:dT, and poly dI:dC were without effect. Among the four synthetic ribonucleotide homopolymers, only poly G at high concentratiorns diminished the light absorption of quinine. Spectral changes caused by the complexing of quinine with DNA were reversed by thermal strand spearation, by Na+, and by Mg++. Results of spectrophotometric titrations of quinine with DNA were used to derive a nonlinear absorption isotherm wihch suggested that the drug binds to more than one class of sites in DNA. Hydrodynamic measurements indicated a decreases in the sedimentation coeffcient and an increase in the viscosity of DNA in the presence of quinine. The inhibition of the DNA polymerase (from Escherichia coli) reaction was a function of the stabilization of the double helix at graded concentrations of quinine. We propose a partial intercalation model of the DNA-quinine complex as a structural hypothesis which is compatible with the results of our hydrodynamic studies, and cite evidence which suggests that the formation of a complex with DNA provides a molecular basis for the antiplasmodial activity of the drug.
- Copyright ©, 1969, by Academic Press Inc.
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