RT Journal Article
SR Electronic
T1 The binding of the anthelmintic pyrvinium cation to deoxyribonucleic acid in vitro.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 427
OP 435
VO 29
IS 4
A1 P Dickie
A1 A R Morgan
A1 D G Scraba
A1 R C von Borstel
YR 1986
UL http://molpharm.aspetjournals.org/content/29/4/427.abstract
AB Pyrvinium pamoate, an anthelmintic drug with mutagenic activity, binds to duplex DNA in vitro. Binding markedly enhances the intrinsic fluorescence of the drug, permitting a characterization of the binding reaction to be performed directly through fluorimetric analysis. The monopyrvinium salt, pyrvinium iodide, binds cooperatively to native calf thymus DNA with an intrinsic binding constant of 1.1 X 10(4) M-1 as determined fluorimetrically and 1.4 X 10(4) M-1 as determined by equilibrium dialysis. The respective binding site was estimated to be 2.5 base pairs. A change in the absorption of bound drug as a function of the binding ratio identifies secondary, nonfluorescent binding which is essentially ionic in character. The binding of pyrvinium removes negative supercoils from PM2-ccc-DNA with an experimental efficiency greater than that observed for the intercalating drug chloroquine. Electron microscopy shows that molecules of pBR322 DNA treated with pyrvinium increase in length by as much as 18% over controls, consistent with an increase in DNA base pair separation upon binding. The evidence indicates that the primary interaction of pyrvinium with DNA involves intercalation.