5'-O-dephosphorylated 2',5'-oligoadenylate (2-5A) with 8-methyladenosine at the 2'-terminus activates human RNase L.

Human ribonuclease L (RNase L), an interferon-induced endoribonuclease, becomes enzymatically active after binding to 2-5A. The 5'-phosphoryl group of 2-5A is reportedly necessary for the conformational change leading to RNase L activation. However, we found that 5'-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2'-terminus were more effective as an activator of RNase L than the parent 2-5A tetramer. Introduction of 8-methyladenosine is thought to induce a dramatic shift of 2-5A in the binding site of RNase L. Copyright (c) 2009 Elsevier Ltd. All rights reserved.