Synthesis and RNase L Binding and Activation of a 2-5A-(5′)-DNA-(3′)-PNA Chimera, a Novel Potential Antisense Molecule

Abstract Fully automated solid-phase synthesis gave access to a hybrid in which 5′-phosphorylated-2′-5′-linked oligoadenylate (2–5A) is connected to the 5′-terminus of DNA which, in turn, is linked at the 3′-end to PNA [2–5A-(5′)-DNA-(3′)-PNA chimera]. This novel antisense molecule retains full RNase L activation potency while suffering only a slight reduction in binding affinity.