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.