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

doi:10.1016/j.bmcl.2009.09.004

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 journal › Article › peer-review

17 Scopus citations

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 language	English (US)
Pages (from-to)	6181-6184
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2009.09.004
State	Published - Nov 1 2009

Keywords

Antisense
Huntingtin
PNA
Peptide nucleic acid

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2009.09.004

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Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine. / Hu, Jiaxin; Dodd, David W.; Hudson, Robert H E et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 21, 01.11.2009, p. 6181-6184.

Research output: Contribution to journal › Article › peer-review

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

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.",

keywords = "Antisense, Huntingtin, PNA, Peptide nucleic acid",

author = "Jiaxin Hu and Dodd, {David W.} and Hudson, {Robert H E} and Corey, {David R.}",

note = "Funding Information: We thank Dr. Filip Wojciechowski for providing the PhpC monomer. This work was supported by grants from the National Institutes of Health ( NIGMS 73042 to D.R.C.), The Robert A. Welch Foundation ( I-1244 to D.R.C.), an award from the McKnight Endowment Fund for Neuroscience (D.R.C.), and the Natural Sciences and Engineering Research Council of Canada (R.H.E.H.). J.H. and D.W.D. contributed equally to this work. ",

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AU - Hudson, Robert H E

AU - Corey, David R.

N1 - Funding Information: We thank Dr. Filip Wojciechowski for providing the PhpC monomer. This work was supported by grants from the National Institutes of Health ( NIGMS 73042 to D.R.C.), The Robert A. Welch Foundation ( I-1244 to D.R.C.), an award from the McKnight Endowment Fund for Neuroscience (D.R.C.), and the Natural Sciences and Engineering Research Council of Canada (R.H.E.H.). J.H. and D.W.D. contributed equally to this work.

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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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KW - Huntingtin

KW - PNA

KW - Peptide nucleic acid

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

Abstract

Keywords

ASJC Scopus subject areas

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