Synthesis of Oligoarginine-Oligonucleotide Conjugates and Oligoarginine-Bridged Oligonucleotide Pairs

Conjugates consisting of oligoarginine peptides linked to oligodeoxynucleotides have been synthesized, including a new type of conjugate, in which a pair of oligonucleotides is bridged by a cationic peptide. Two different 9-mer oligonucleotides were conjugated to the terminal cysteine residues of the peptide series H-Cys-(Arg)_n-Cys-NH₂ (n = 3,5,7). Different thiol protecting groups were utilized on the amino- and carboxy-terminal cysteine residues of the peptide to allow selective attachment to the 3′- or 5′-terminus of each specific oligonucleotide. The conjugates containing oligoarginine peptides were purified by anion-exchange chromatography, and their structures were confirmed by polyacrylamide gel electrophoresis and amino acid analysis.