A new and potent 2-5A analogue which does not require a 5′-polyphosphate to activate mouse L-cell RNase L

Abstract In order to explore the possibility of supplanting the requirement of a 5′-triphosphate moiety for the activation of the 2-5A-dependent endonuclease (RNase L) of mouse L-cells, two new tetrameric analogues of 2-5A were synthesized. The first tetramer, obtained by both a modified prebiotic synthetic approach as well as a phosphite triester solid phase oligonucleotide synthesis method, was p5′A2′p5′A2′p5′(br 8 A)2′p5′(br 8 A). The second oligonucleotide was derived from the former by a sequence involving periodate oxidation, reaction with n -terminal adenosine residue to 9-(3′-aza-4′-hexyl-1′,2′,3′,4′-tetradeoxyhexopyranos-l 1 -yl)-8-bromoadenine. Both of these oligomers, bearing only 5′-monophosphate groups, were found to be as potent as 2-5A itself as activators of the RNase L of mouse L-cells.