2-methyladenosine-substituted 2′,5′-oligoadenylates:: Conformations, 2-5A binding and catalytic activities with human ribonuclease L

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. (C) 2000 Elsevier Science Ltd. All rights reserved.