Introduction of Chirality into PNA By Replacement of the Achiral Methylene Carbonyl Linkage to the Nucleobase

Abstract

A novel approach to the introduction of chirality into peptide nucleic acid (PNA) by replacement of the methylene carbonyl linker by an alpha-amino acid derived moiety is described. A monomer compatible with Fmoc-based oligomerization chemistry possessing an L-serine derived linker has been synthesized and incorporated into PNA oligomers. A single, central substitution in a hexathymine PNA strongly destabilized triple helix formation whereas a central substitution in a mixed sequence is much better tolerated. We have investigated the influence of this substitution on the selectivity for strand composition (DNA versus RNA complement) and strand orientation (antiparallel versus parallel) in the context of duplex formation. A PNA 11-mer with a single substitution demonstrates a preference for an antiparallel RNA complement, as judged by thermal denaturation analysis of the complexes.

Keywords:

• Peptide nucleic acid
• PNA
• chirality
• L-serine
• PNA oligomers

Acknowledgments

The authors wish to thank NSERC (Canada), the Canadian Foundation for Innovation, and the University of Western Ontario through the Academic Development Fund for support of this work.