Cellular Localization and Allele-selective Inhibition of Mutant Huntingtin Protein by Peptide Nucleic Acid Oligomers Containing the Fluorescent Nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine
Bioorganic & Medicinal Chemistry Letters
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Peptide nucleic acid (PNA) is a successful DNA/RNA mimic. A major challenge for research is to invent chemically modified PNAs that retain the favorable properties of the parent compound while improving biological recognition. Here, we test modified PNAs containing [bis-o-(aminoethoxy)phenyl]pyrrolocytosine bases designed to engage guanine with an additional hydrogen bond. We observe elevated melting temperatures, localization to cellular compartments, and allele-selective inhibition of mutant huntingtin protein expression.