Synthesis of double-Headed 2-5A-Antisense chimeras and Their ability to activate human RNase L

The synthesis of a novel 2-5A-antisense chimera having two molecules of a 2-5A tetramer at the 5′-terminus of the antisense moiety with a 2-(hydroxymethyl)-1,3-propanediol linker is described. The ability of the synthesized 2-5A antisense chimeras to activate RNase L was estimated by monitoring the cleavage of a target RNA by the activated RNase L. The double-headed 2-5A-antisense chimera linked with two molecules of a butanediol linker more efficiently cleaved the target RNA as compared with the single-headed 2-5A-antisense chimera and the double-headed 2-5A-antisense chimera linked with a molecule of the butanediol linker.