In order to facilitate the removal of peptide nucleic acid (PNA), when necessary, from its duplexes and invasion complexes, a disulfide bond was introduced to its main chain. The disulfide bond was readily cleaved by various reducing agents (2-mercaptoethanol, DL-dithiothreitol, and tris(2-carboxyethyl)phosphine) even when the PNA was forming a duplex with its complementary DNA. The resultant two short PNA fragments were spontaneously removed from the DNA. Double-duplex invasion complexes of two disulfide-containing PNA strands were also promptly cleaved by the reducing agents. By using this modified PNA, a desired DNA fragment was picked up from DNA mixtures, and obtained in a pure form (free from the PNA) by the reductive treatment. Importantly, this separation was achieved at low temperatures (e.g., 37 °C), where all the DNAs (and other biomolecules if any) should be kept intact. Strong potential of the modified PNA for various biological applications has been indicated.