Molecular Pharmacology, Vol 6, 548-556, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Chloroquine on the Enzymatic Hydrolysis of Nucleic Acids

¹ Center for Research in Pharmacology and Toxicology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514

Chloroquine stimulates the hydrolysis of soluble RNA by pancreatic ribonuclease and micrococcal nuclease, enzymes that are primarily endonucleases. The addition of MgCl₂, at low concentrations relative to the concentrations of RNA nucleotides, does not appreciably affect the extent of the stimulation. Stimulation by chloroquine does not appear to be due to a change induced by the drug in the tertiary structure of soluble (on transfer) RNA, since the hydrolysis of the single-stranded copolymer of riboadenylate and ribocytidylate is also stimulated by chloroquine. Chloroquine inhibits the hydrolysis of soluble RNA and polyadenylate by spleen phosphodiesterase, an exonuclease. Chloroquine also inhibits the hydrolysis of native (double-stranded) and heat-denatured (single-stranded) DNA by micrococcal nuclease and, in agreement with other reports, hydrolysis by pancreatic deoxyribonuclease.