Synthesis of ribonucleic guanidine: replacement of the negative phosphodiester linkages of RNA with positive guanidinium linkages

Replacement of the negatively charged phosphodiester linkages of RNA with positively charged guanidinium linkages provides the polycationic ribonucleic guanidine (RNG). RNG is designed to bind strongly to target DNA/RNA through the specific interactions of nucleobases and the attractive electrostatic interactions of backbones, thus RNG is a putative antisense/antigene agent. Preparation of uridine and adenine building blocks for the RNG synthesis, as well as the stepwise synthesis of oligomeric RNG are reported. Pentameric homo uridyl, adenyl, and a pentameric mixed base sequence have been synthesized. The methods were also applied to a convenient solid-phase synthesis of RNG.