Abstract

Peptide nucleic acids (PNAs) are getting more and more attention as nucleic acid mimics, in which the backbone is a N-(2-aminoethyl)glycine unit instead of the sugar phosphodiester. PNAs hybridize to complementary DNA or RNA following the Watson-Crick base-pairing rules, but with higher affinity and sequence selectivity compared to their natural counterparts. Despite these advantages and the simplicity of PNA synthesis, the major drawback is their relatively low solubility in aqueous solutions. 1 This disadvantage can be circumvented by the incorporation of diethylene glycol in γ-position of the backbone (γ-miniPEG-PNA). 2 The design and synthesis of model peptide nucleic acids and γ-miniPEG-PNAs will be shown. The characterization of RNA mimics will be shown using mass spectrometry. The hybridization of selected RNA/PNA and RNA/(γ-miniPEG-PNA duplexes will be presented using surface plasmon resonance spectroscopy.1. Thomson, S. A.; Josey, J. A.; Cadilla, R.; Gaul, M. D.; Fred Hassman, C.; Luzzio, M. J.; Pipe, A. J.; Reed, K. L.; Ricca, D. J.; Wiethe, R. W.; Noble, S. A., Fmoc mediated synthesis of Peptide Nucleic Acids. Tetrahedron 1995, 51 (22), 6179-6194.2. Sahu, B.; Sacui, I.; Rapireddy, S.; Zanotti, K. J.; Bahal, R.; Armitage, B. A.; Ly, D. H., Synthesis and Characterization of Conformationally Preorganized, (R)-Diethylene Glycol-Containing γ-Peptide Nucleic Acids with Superior Hybridization Properties and Water Solubility. The Journal of Organic Chemistry 2011, 76 (14), 5614-5627.