Tailoring Peptide Nucleic Acids for Enhanced RNA-Targeting

Abstract

Peptide nucleic acids (PNAs) represent nucleic acid mimics featuring a peptide backbone composed of N-(2-aminoethyl)glycine units, deviating from the conventional sugar-phosphate core. They have gained notice due to their ability to establish high-affinity hybridization complexes with complementary RNA or DNA, demonstrating enhanced sequence selectivity and resilience against disintegration by proteases and nucleases.(1) Despite these favorable features, the intrinsic poor water solubility of PNAs restricts their implementation in biological systems, posing concerns about potential cytotoxicity. Overcoming this limitation, the concept of γ-miniPEG-PNA incorporates diethylene glycol groups throughout the PNA backbone.(2) Various model PNAs and γ-miniPEG-PNAs are synthesized utilizing solid-phase peptide synthesis and characterized by mass spectrometry. Hybridization dynamics of selected RNA/PNA and RNA/γ-miniPEG-PNA duplexes are elucidated, employing surface plasmon resonance spectroscopy.

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