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PNAs embedding NLS peptide
6.2 Results and discussion
6.2.1 PNA design and synthesis
Recently, it has been demonstrated that PNAs bearing ad hoc modifications within the
backbone have enhanced nuclear uptake properties, comparable to those linked to carrier
peptides. In particular, chiral PNAs having arginine-modified monomers were demonstrated
to concentrate in the nucleus upon uptake experiments (like poly arginine peptides) 25,26 due to
the positive charges of the arginine side chains.
These crude preliminary experiments demonstrate that backbone derivatization of PNAs can
be exploited in order to create more complex systems, characterized by new properties typical
of aminoacidic sequences. In fact, a particularly fascinating, but seldom explored, aspect of
PNAs, is their “double nature”: PNAs are not only able to recognize through the nucleobases
a complementary DNA sequence (a property typical of nucleic acids), but they also possess a
pseudopeptidic backbone and therefore might potentially display properties similar to those
performed by proteins. The backbone can be, indeed, considered as a long sequence of
pseudoglycylglycine dipeptides, therefore a mimic of a polyGly protein. In order to express
all the “proteic potential” of PNAs, the backbone should be modified in order to become a
real peptide mimic, by inserting amino acid-derived side chains in positions 2 and 5 (Figure 6-
2). In this way, a real “peptide” and “nucleic acid” could be obtained, fully exploiting the
intrinsinc double nature of the molecule.
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