Sequence-specific RNA cleavage by oligonucleotide-peptide conjugates

This paper considers the site-directed cleavage of the in vitro transcript of human tRNALys3 by the conjugate CNH2Gly(ArgLeu)3ArgLeuN—p-DAG—5"CCCTGGACCCTCAGAT3" (conjugate pep-1A) of the oligodeoxyribonucleotide 1A (CCCTGGACCCTCAGAT) with a peptide [LeuArg]4Gly attached at the 5" terminus of the oligonucleotide through diethylene glycol as a linker. Under physiological conditions, the conjugate pep-1A cleaved the C56-A57 phosphodiester bond of the RNA target with high efficacy. In addition, the conjugate cleaved several other bonds in the D loop, at the basis of the amino-acceptor stem, and in the anticodon hairpin due, probably, to the formation of imperfect complexes of the conjugate with partially complementary sequences in the RNA structure.