Synthesis and evaluation of a novel guanidinium linked oligonucleotide is described. Replacement of the anionic phosphate backbone with cationic guanidinium linkages should increase the affinity of the ligand for duplex DNA and form a more stable triple helical structure. The internucleoside guanidinium will be formed by the nucleophilic attack of a solid support bound 5'-amine on either a 3'-carbodiimide or a 3'alkylated thiourea. Triple helix behavior will be evaluated using UV melting experiments, the gel mobility shift assay, and hydroxyl radical footprintng.
