We and others have demonstrated the use of triaminotriazine (melamine) as a synthetic base-triple motif in a family of molecules we call bifacial peptide nucleic acid (bPNA). Bifacial PNA engages two oligo T/U strands simultaneously to form a unique triple stranded structure. bPNAs can serve as allosteric triggers of aptamer protein-binding, ribozyme catalysis, aptamer small-molecule binding and scaffolds for potent siRNA delivery. Peptoid, polyacrylate and small molecules have all been demonstrated to be functional bPNAs. Small molecules displaying melamine can target T/U bulges in folded nucleic acid structures and trigger cooperative folding in unstructured oligo T/U domains. This targeting strategy has been applied to develop fluorogen sensing G-quadruplex based RNA aptamers and NMR-probes for RNA-binding protein domains. Overall, a wide range of applications emerge from the use of a simple artificial base triple unit.