Role of purine N-3 in the biologic activities of poly(A) and poly(I)

Abstract

Poly(c³A) (poly 3-deazaadenylic acid) and poly(c³I) (poly 3-deazainosinic acid) differ in biological reactivity from their parent compounds poly(A) and poly(I) and from their 7-deaza counterparts poly(c⁷A) and poly(c⁷I). Three parameters of biological reactivity were evaluated : (1°) interferon induction, (2°) anti-complement activity, (3°) reverse transcriptase inhibition. Unlike poly(A).poly(U), poly(I).poly(C) and poly(I).poly(br⁵C), the mixtures of poly(c³A) + poly(U), poly(c³I) + poly(C), and poly(c³I) + poly(br⁵C) failed to elicit an interferon response in “superinduced” primary rabbit kidney cells. Poly(I) and its analogs poly(c³I) and poly(c⁷I) inhibited hemolytic complement activity, whereas poly(A) and its analogs poly(c³A) and poly(c⁷A) failed to do so. Both poly(I) and poly(c⁷I), but not poly(c³I), lost their anti-complement potency when annealed to either poly(C) or poly(A).poly(U). Similarly, poly(I) and poly(c⁷I), but not poly(c³I), suppressed the interferon inducing ability of poly(A).poly(U), suggesting that both poly(I) and poly(c⁷I), but not poly(c³I), added to poly(A).poly(U) to form a triple-helical structure. Poly(I), poly(c⁷I) and poly(c⁷A) exerted a distinct inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity of murine leukemia virus, while under the same conditions poly(c³I) and poly(c³A) showed little, if any, inhibitory effect.