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We previously demonstrated that an antisense 2'-O-methyloligonucleotide, with two terpyridine*Cu(II) complexes at contiguous internal sites, was highly active as a sequence-specific artificial ribonuclease. Two kinds of terpyridine-linked uridine derivatives (Ut and tU(L)) were used for its construction, and the residue on the 5'-side (Ut) was the derivative with terpyridine attached to the 2'-oxygen via a short linker arm. To examine the structure-activity relationship of this type of RNA cleaver, we synthesized an analogous RNA cleaver with the inosine counterpart (It) on the 5'-side, since inosine can base-pair with A, U or C. Using the RNA cleavers and the RNA oligomer substrates, we examined the effect of base-pair formation at the Ut (or It) and tU(L) sites on the activities of the cleavers. The cleavage reactions revealed that, for this type of RNA cleaver, a base-pair at the 5'-side and no base-pair at the 3'-side were required for high activity. In addition, for the 5'-side-It residue, a normal base-pair (I-C pair) was needed.

Structure-activity relationship of an antisense oligonucleotide-two Cu(II) complex conjugate as an artificial ribonuclease