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PNAs: from birth to adulthood
between the 2’oxygen and the 4’ carbon of the ribose ring 6 . Pure LNA oligonucleotides can
be used, as well as mixed oligonucleotides with standard DNA monomers and LNA
monomers, obtaining an increased affinity for DNA and RNA, and resistance to enzymes. The
good cellular uptake also allowed applications in gene therapy with good results 7 . In
morpholino oligonucleotides (MF), the ribose ring is replaced by a morpholino moiety and
phosphoroamidate linkages are used instead of phosphodiester bonds 8 . The affinity for
complementary sequences is similar to that of DNA oligonucleotides, the enzymatic stability
is high and unspecific interactions with proteins are not observed, allowing for their use for
in-vivo applications. Cyclohexene nucleic acids (CeNA) 9 , tricyclo-DNA (tcDNA) 10 , 2’-
deoxy-2’-fluoro-β-D-arabino nucleic acid (FANA) 11 are other types of DNA analogues which
show an increased affinity towards DNA and RNA, if compared to standard oligonucleotides.
The affinity usually increases because of the absence of negative charges in the backbone,
avoiding electrostatic repulsions with the target DNA strand, or for the introduction of more
rigid groups, able to maintain the correct nucleobase orientation to form Watson-Crick
interactions. The increase of in vivo stability usually observed is due to the inability of
degrading enzymes to recognize the modified structures 12 .
1.3 PNA
The quest for the development of a high performance DNA analogue led in 1991 to the
synthesis of another type of modified nucleic acids, called Peptide Nucleic Acids (PNAs) 13 .
PNA
DNA
Figure 1-2: Comparison of PNA and DNA chemical structures (P. E. Nielsen et al., Science, 1991,
254, 1497)
This class of nucleic acid analogues has been obtained by completely changing the DNA
backbone chemistry. The classical sugar-phosphate backbone, in fact, has been replaced with
9