Peptide Nucleic Acid (PNA) is conceptually a DNA analog, but in a chem
ical sense PNA bridges peptides and nucleic acids by virtue of its pse
udopeptide backbone and its nucleobases. Since this mimic was introduc
ed five years ago, convenient synthetic routes to PNA monomers as well
as oligomers have been devised, and a number of structural modificati
ons have been introduced into PNA. In addition, extensive research has
shed light on the interesting properties of PNA, demonstrating the de
velopment potential of PNA into biomolecular tools, as well as antisen
se and/or antigene drugs. This review focuses primarily on the chemica
l aspects of PNA and its modifications, including the introduction of
chirality, the elongation of the pseudopeptide backbone as well as the
permutation of functional groups within the backbone, and the introdu
ction of a non-natural nucleobase. In addition, the effects of covalen
tly linking two PNA oligomers will be described. Furthermore, the abil
ity of PNA to hybridize to DNA or RNA targets with a high sequence spe
cificity will be discussed, as will the secondary structure of such hy
brids and that of PNA itself. Finally, (potential) applications of PNA
are briefly dealt with herein.