The modeling, synthesis, and characterization of oligomers containing 2-aminoquinazolin-5-yl 2'-deoxynucleotide residues are reported. The 2-arninoquinazoline residues sequence specifically bind via Hoogsteen base pairing as a third strand in the center of the major groove at TA base pair Watson-Crick duplex sequences. Evidence for the formation of a sequence specific three-stranded structure is based on thermal denaturation UV-vis and fluorescence studies. The novel 2-aminoquinazoline C-nucleoticle is a component of a system designed to overcome the homopurine requirement for triple helix structures.