Efficient guanidination of the phosphate linkage towards cationic phosphoramidate oligonucleotides

An efficient postsynthesis method of guanidination of oligonucleotides was employed to introduce several guanidinium groups into internucleotide phosphoramidate linkages. The amino functions of aminobutylphosphoramidate links were converted to guanidine butylphosphoramidates using a solution of O-methylisourea hemisulfate in aqueous ammonia, in a short reaction time. The synthesis of various fully guanidylated oligonucleotides was successfully performed to provide a new class of cationic phosphoramidate oligonucleotides.