Synthesis of Fluorine-Labeled Peptide Nucleic Acid Building Blocks as Sensors for the 19F NMR Spectroscopic Detection of Different Hybridization Modes

Abstract

Peptide nucleic acid (PNA) building blocks, bearing a fluorine sensor at C-5 of the uracil base [viz. trifluoromethyl and 3,3-bis(trifluoromethyl)-4,4,4-trifluorobut-1-ynyl], were synthesized and incorporated to a PNA strand, and their applicability for the monitoring of different hybridization modes by (19)F NMR spectroscopy was studied. Both sensors gave unique (19)F resonance shifts in NMR when the PNA was targeted to a complementary antiparallel DNA, antiparallel RNA, parallel DNA, and parallel RNA. The 5-trifluoromethyl-derived sensor was additionally applied for the monitoring of interconversions from a parallel DNA/PNA complex to an antiparallel RNA/PNA complex and from a PNA/PNA complex to two DNA/PNA complexes (i.e., double-duplex invasion).