Synthesis of a C-linked glycosylated thymine-based PNA monomer and its incorporation into a PNA oligomer

Abstract

Backbone modification of peptide nucleic acids (PNAs) by glycosylation has been shown to enhance selective biodistribution and cellular targeting of PNA oligomers based on sugar and cell surface lectin interactions. Here we report the synthesis of a new backbone-glycosylated thymine-based PNA monomer (T^gal). The sugar residue was attached to the backbone of PNA via a stable carbon–carbon linkage between the sugar and the PNA monomers. Also, incorporation of the modified monomer into a PNA decamer (H-Ala^gal-G-G-G-T^gal-C-A-G-C-T^gal-T-Lys-NH₂) was successfully performed. Melting temperature (UV-T_m) of the modified PNA against the complementary DNA was only slightly lower than unmodified PNA.