Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine

Jiaxin Hu, David W. Dodd, Robert H E Hudson, David R. Corey

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6181-6184
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number21
DOIs
StatePublished - Nov 1 2009

Fingerprint

Peptide Nucleic Acids
Guanine
Mutant Proteins
Oligomers
Freezing
Melting point
Hydrogen
Hydrogen bonds
Alleles
RNA
Temperature
DNA
Research
Proteins
(bis-o-(aminoethoxy)phenyl)pyrrolocytosine
Huntingtin Protein

Keywords

  • Antisense
  • Huntingtin
  • Peptide nucleic acid
  • PNA

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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AU - Corey, David R.

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AB - 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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