2-Methyladenosine-Substituted 2',5'-oligoadenylates: conformations, 2-5A binding and catalytic activities with human ribonuclease L.

Abstract 2-Methyladenosine-substituted analogues of 2-5A, p5′A2′p5′A2′p5′(me 2 A), p5′(me 2 A)2′p5′A2′p5′A, and p5′(me 2 A)2′p5′(me 2 A)2′p5′(me 2 A), were prepared via a modification of a lead ion-catalyzed ligation reaction. These 5′-monophosphates were subsequently converted into the corresponding 5′-triphosphates. Both binding and activation of human recombinant RNase L by various 2-methyladenosine-substituted 2-5A analogues were examined. Among the 2-5A analogues, p5′A2′p5′A2′p5′(me 2 A) showed the strongest binding affinity and was as effective as 2-5A itself as an activator of RNase L. The CD spectra of both p5′(me 2 A)2′p5′A2′p5′A and p5′A2′p5′A2′p5′(me 2 A) were superimposable on that of p5′A2′p5′A2′p5′A, indicative of an anti orientation about the base-glycoside bonds as in naturally occurring 2-5A.