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

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 (T_m). It was found that the T_m 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.