New Synthetic Route to γ-Mercaptomethyl PNA Monomers

Abstract

Peptide nucleic acids (PNAs) are oligonucleotide mimics widely used as antisense, antigene molecules, and biotechnological tools. Recently, several microarrays and other biosensors based on PNAs have been developed. The construction of PNA molecular beacons or light-up probes for DNA detection requires the labelling of the PNA moiety. Labels are usually attached at the C or N terminal end by a flexible linker or in the middle of a PNA sequence, substituting one PNA base with an artificial base or by attaching fluorophores to a modified PNA backbone. The need to develop simple protocols to label PNAs encouraged us to design a new procedure for the synthesis of γ-mercaptomethyl-modified PNA. Here we propose a new strategy for the synthesis of modified PNAs, bearing amino acid side chains. The synthesis is straightforward and is an improvement to the procedures reported so far, as it uses stable intermediates and proceeds with better yields.

Keywords:

• Amino acid
• PNA
• synthesis

ACKNOWLEDGMENTS

This work was supported by the Ministero dell'Università e della Ricerca, Programmi di ricerca di Rilevante Interesse Nazionale (MUIR PRIN05) grant. The authors are grateful to G. Perretta and L. Zona for technical assistance.