Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine |
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| Authors: | Jiaxin Hu David W Dodd Robert HE Hudson David R Corey |
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| Institution: | 1. Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, 6001 Forest Park Road, TX 75390, USA;2. Department of Biochemistry, UT Southwestern Medical Center at Dallas, Dallas, 6001 Forest Park Road, TX 75390, USA;3. Department of Chemistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7 |
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| Abstract: | 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. |
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