Role of purine N-3 in the biologic activities of poly(A) and poly(I).
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 degree) interferon induction, (2 degrees) anti-complement activity, (3 degrees) 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 "super-induced" 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 turine leukemia virus, while under the same conditions poly(c3I) and poly(c3A) showed little, if any, inhibitory effect.
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D007291:Inosine Monophosphate / Q000378:metabolism; D007369:Interferon Inducers / Q000032:analysis; D007668:Kidney / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000201:enzymology; D011061:Poly A / Q000378:metabolism*; D011066:Poly C / Q000031:analogs & derivatives / Q000378:metabolism; D011069:Poly I / Q000378:metabolism*; D011072:Poly U / Q000378:metabolism; D011119:Polynucleotides / Q000378:metabolism; D011131:Polyribonucleotides / Q000378:metabolism*; D011687:Purines; D011758:Pyrroles / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011817:Rabbits; D012265:Ribonucleotides / Q000378:metabolism; D013329:Structure-Activity Relationship
D007369:Interferon Inducers; D011119:Polynucleotides; D011131:Polyribonucleotides; D011687:Purines; D011758:Pyrroles; D012265:Ribonucleotides; D007291:Inosine Monophosphate; D011061:Poly A; D011069:Poly I; D011072:Poly U; D011066:Poly C; D003165:Complement System Proteins; D012194:RNA-Directed DNA Polymerase