Document Detail

Peptide nucleic acids conjugated to short basic peptides show improved pharmacokinetics and antisense activity in adipose tissue.
MedLine Citation:
PMID:  20420385     Owner:  NLM     Status:  MEDLINE    
A peptide nucleic acid (PNA) targeting a splice junction of the murine PTEN primary transcript was covalently conjugated to various basic peptides. When systemically administered to healthy mice, the conjugates displayed sequence-specific alteration of PTEN mRNA splicing as well as inhibition of full length PTEN protein expression. Correlating activity with drug concentration in various tissues indicated strong tissue-dependence, with highest levels of activity observed in adipose tissue. While the presence of a peptide carrier was found to be crucial for efficient delivery to tissue, little difference was observed between the various peptides evaluated. A second PNA-conjugate targeting the murine insulin receptor primary transcript showed a similar activity profile, suggesting that short basic peptides can generally be used to effectively deliver peptide nucleic acids to adipose tissue.
Edward V Wancewicz; Martin A Maier; Andrew M Siwkowski; Klaus Albertshofer; Theodore M Winger; Andres Berdeja; Hans Gaus; Timothy A Vickers; C Frank Bennett; Brett P Monia; Richard H Griffey; Christopher J Nulf; Jiaxin Hu; David R Corey; Eric E Swayze; Garth A Kinberger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-22     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3919-26     Citation Subset:  IM    
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MeSH Terms
Adipose Tissue / metabolism*
Cell Line
Drug Carriers
Kidney / metabolism
Liver / metabolism
Mice, Inbred BALB C
Oligopeptides / chemistry*
PTEN Phosphohydrolase / biosynthesis*,  genetics
Peptide Nucleic Acids / administration & dosage,  chemistry,  pharmacokinetics,  pharmacology*
RNA Splice Sites
RNA Splicing
RNA, Antisense / administration & dosage,  chemistry,  pharmacokinetics,  pharmacology*
RNA, Messenger / biosynthesis,  genetics
Receptor, Insulin / biosynthesis*,  genetics
Structure-Activity Relationship
Tissue Distribution
Grant Support
60642//PHS HHS; 73042//PHS HHS; R01 GM060642/GM/NIGMS NIH HHS; R01 GM060642-01/GM/NIGMS NIH HHS; R01 GM073042/GM/NIGMS NIH HHS; R01 GM073042-01/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Drug Carriers; 0/Oligopeptides; 0/Peptide Nucleic Acids; 0/RNA Splice Sites; 0/RNA, Antisense; 0/RNA, Messenger; EC, Insulin; EC protein, mouse; EC Phosphohydrolase

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