We report herein DNA- and RNA-templated chemical transformation of bifacial peptide nucleic acid (bPNA) fragments directed by an abiotic triplex hybrid interface. Assembly of one bPNA strand with two unstructured oligo T/U strands enables facile insertion of DNA and RNA template sites within partially folded nucleic acids; this template topology is not easily accessed through native base-pairing. Triplex hybridization of reactive bPNA fragments on DNA and RNA templates is shown to catalyze amide bond ligation and controlled bPNA chain extension. RNA-templated oxidative coupling of bPNA fragments is found to result in the emergence of ribozyme cleavage function, thus establishing a connection between engineered and native reaction sites. These data demonstrate the use of new topologies in nucleic acid-templated chemistry that could serve as chemically sensitive DNA and RNA switches.