S. Sforza et al.
SHORT COMMUNICATION
tide sequence encrypted in the backbone of the modified
PNA can behave as a fully functional peptide mimic, shed-
ding light on a new dimension concerning the properties of
PNAs, which may find numerous applications in bioorganic
chemistry and molecular biology. For example, a PNA with
the embedded NLS sequence could be used to efficiently
translocate the PNA in the cell nuclei after injection in the
blood stream, avoiding degradation from serum proteases,
as it may happen when the NLS sequence is simply linked
as a normal peptide at the C-terminus. In more general
terms, a peptide nucleic acid possessing the functionalities
of the proteins might be potentially used to develop PNAs
endowed with catalytic functions, fully exploiting their in-
trinsic nucleic acid and peptide natures. More experiments
are needed to obtain long PNAs enclosing these modified
monomers at one terminus to verify their binding properties
towards complementary nucleic acids.
Figure 3. Fluorescence microscopy analysis (left) of uptake of
RH30 cells treated for 3 h with NLS peptide 1. Optical images are
also reported (right).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, LC/ESI-MS and LC/UV profiles of com-
pounds 1–3.
Acknowledgments
This work was partially supported by grants from the Ministero
dellЈUniversità e della Ricerca (MIUR) (PRIN2005, Grant No.
2005038704, and PRIN2007, Grant No. 2007F9TWKE).
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Figure 4. Fluorescence microscopy analysis (left) of uptake of
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Received: January 29, 2010
Conclusions
In conclusion, we have demonstrated the chemical feasi-
bility of synthesizing peptide nucleic acids containing em-
bedded amino acid side chains in their backbone that mimic
a complex peptide sequence. The preliminary data here on
the NLS-mimicking PNA demonstrate that the pseudopep-
Published Online: March 24, 2010
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Eur. J. Org. Chem. 2010, 2441–2444