Oligonucleotide—Poly-L-ornithine Conjugates: Binding to Complementary DNA and RNA

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Abstract
On the basis of the reported enhanced antisense activity of polylysine—oligonucleotide conjugates, a synthetic 12-mer oligodeoxyribonucleotide has been coupled at its 5′ terminus to a series of positively charged (δ-ornithine)ncysteine peptides. Binding between the nucleic acid—peptide conjugate and its complementary DNA target sequence was detected by the impact of complexation on the melting temperature (Tm). It was found that the Tm for the nucleic acid—peptide gradually increased with increasing net charge on the conjugated peptide. Site-directed cleavage with RNase H demonstrates that the peptide-modified oligomer also hybridizes with its RNA target sequence. Increased affinity for target mRNA with net charge was shown by a cell-free translation arrest assay.