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

卷:19

Article

Hua, Jiaxin^2,3  Dodd, David W.¹  Hudson, Robert H. E.¹  Corey, David R.^2,3 

[1] Univ Western Ontario, Dept Chem, London, ON N6A 5B7, Canada

[2] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

关键词: Peptide nucleic acid;    Antisense;    PNA;    Huntingtin;   

DOI  :  10.1016/j.bmcl.2009.09.004

来源: Elsevier

【 摘 要 】

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. (c) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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