Cellular Localization and Allele-selective Inhibition of Mutant Huntingtin Protein by Peptide Nucleic Acid Oligomers Containing the Fluorescent Nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine

Authors

Jiaxin Hu, UT Southwestern Medical Center at Dallas
David W. Dodd, UT Southwestern Medical Center at Dallas
Robert H. E. Hudson, University of Western Ontario
David R. Corey, UT Southwestern Medical Center at Dallas

Document Type

Article

Publication Date

11-2009

Journal

Bioorganic & Medicinal Chemistry Letters

Volume

19

Issue

21

First Page

6181

Last Page

6184

URL with Digital Object Identifier

10.1016/j.bmcl.2009.09.004

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.