Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine.
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.
Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, 6001 Forest Park Road, TX 75390, USA.
Jiaxin
J
Hu
David W
DW
Dodd
Robert H E
RH
Hudson
David R
DR
Corey
D000483:Alleles; D002460:Cell Line; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D000071058:Huntingtin Protein; D006860:Hydrogen Bonding; D050505:Mutant Proteins / Q000032:analysis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D044366:Transition Temperature
C546156:(bis-o-(aminoethoxy)phenyl)pyrrolocytosine; D005456:Fluorescent Dyes; C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020135:Peptide Nucleic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D003596:Cytosine