Selectivity of the cleavage of single stranded over hybridized forms of internally modified disulfide–peptide nucleic acids
(PNA) has been optimized using a series of phosphines and thiols, which have different sizes and charges. For the most selective
cleaver found (tris-(carboxyethyl)-phosphine), reactivity of single stranded PNA is 33 times higher than that of the PNA–DNA
duplex. Selectivity of single stranded disulfide–PNA cleavage has been explained in terms of electrostatic interaction between the
substrate and the cleaver.