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  CPP or Cholesterol Conjugated Antisense PNA for Cellular Delivery

Joshi, R., Mishra, R., Su, W., & Engelmann, J. (2008). CPP or Cholesterol Conjugated Antisense PNA for Cellular Delivery. Poster presented at 30th European Peptide Symposium (30 EPS), Helsinki, Finland.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-C767-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-8B95-8
Genre: Poster

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 Creators:
Joshi, R1, 2, Author              
Mishra, R1, 2, Author              
Su, W1, 2, Author              
Engelmann, J1, 2, Author              
Affiliations:
1Former Department MRZ, Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_2528700              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Peptide nucleic acid (PNA) is a DNA mimic consisting of the four common bases of DNA on a pseudopeptide backbone that makes it extremely stable in biological fl uids. Antisense PNA is targeted against mRNA in cytoplasm in a sequence specifi c manner. However, the main hindrance to the effective use of PNAs has been their relatively poor uptake by cells. Endosomal release or direct uptake into cytosol of agents is mandatory for attaining mRNA based targeting. There are reports on the cell penetrating peptide (CPP) based delivery system. It has also been reported that conjugates of cholesterol and siRNAs facilitate cellular import (1). The aim of this study was to synthesize different sequences of cholesterol coupled antisense PNA and to compare its uptake characteristics with a CPP-PNA conjugate. The synthesis of PNA (anti-dsRed PNA (agcgcctgtacc), specifi cally targeted to mRNA of dsRed, a red fl uorescent protein) conjugated to CPP (d-Tat) or cholesterol was performed in fully automated synthesizer (Prelude, Protein Technologies, Inc.) using continuous solid phase chemistry. To increase the solubility in water, linkers (AEEA) and additional charged amino acids were coupled or the sequence of peptide, PNA and cholesterol was changed. All compounds were labelled with FITC to confi rm the cellular uptake by fl uorescence microscopy and spectroscopy. Cell uptake studies showed that the CPP bound PNA was located predominantly in vesicles indicating an endosomal uptake mechanism and subsequent entrapment in vesicles. Cholesterol bound PNA was also effi ciently internalized. However, it was also located inside vesicles without detectable cytosolic distribution. PNA-Cholesterol has fewer synthetic steps than PNA-CPP. However, it was also located inside vesicles restricting its applicability for mRNA targeting. The effi cient uptake might make it a promising cellular delivery agent after further improvements.

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 Dates: 2008-10
 Publication Status: Published in print
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 Identifiers: DOI: 10.1002/psc.1090
BibTex Citekey: 5373
 Degree: -

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Title: 30th European Peptide Symposium (30 EPS)
Place of Event: Helsinki, Finland
Start-/End Date: 2008-08-31 - 2008-09-05

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Title: Journal of Peptide Science
  Other : J. Peptide Sci.
Source Genre: Journal
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Publ. Info: Chichester, West Sussex, UK : John Wiley & Sons
Pages: - Volume / Issue: 14 (Supplement 1) Sequence Number: P41925-056 Start / End Page: 157 Identifier: ISSN: 1075-2617
CoNE: https://pure.mpg.de/cone/journals/resource/954925604784