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  Cell Penetrating Peptides Delivering Intracellular Targeted Agents for Molecular Imaging

Mishra, R., Su, W., Brud, A., Sauer, M., Pfeuffer, J., Ugurbil, K., et al. (2008). Cell Penetrating Peptides Delivering Intracellular Targeted Agents for Molecular Imaging. 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-C765-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-8B8F-0
Genre: Poster

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 Creators:
Mishra, R1, 2, Author              
Su, W1, 2, Author              
Brud, A1, 2, Author              
Sauer, MG, Author
Pfeuffer, J, Author              
Ugurbil, K, Author
Engelmann, J1, 2, Author              
Affiliations:
1Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              
2Former Department MRZ, Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_2528700              

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 Abstract: Cell penetrating peptides (CPP) are a special class of peptides that possess the property to traverse the formidable barrier of the plasma membrane and deliver cargos into cells. Using CPP as vectors and DNA, mRNA or proteins/enzymes as potential intracellular targets, a new generation of intracellular contrast agents (CAs) can be developed. These agents have prospective use for molecular imaging (both optical and magnetic resonance imaging) by targeted labeling of cells. Aiming to image the presence of specifi c mRNAs or enzymes, two mRNA targeting (contains a PNA sequence antisense or non-sense to the target mRNA of DsRed) and one enzyme targeted (contains a unit cleavable by -galactosidase) CAs were tested for their activity in the presence and absence of respective targets. The antisense targeting CA, their nonsense derivative and the enzyme targeted CA were taken up effi ciently into cells by an exclusively endosomal mechanism as observed by fl uorescence microscopy. Cell free binding assays proved a specifi c interaction with a synthetic target for the antisense but not for non-sense CA. Magnetic Resonance studies showed a higher uptake in transgenic DsRed expressing cells than the parent cells. However, no difference was observable for antisense versus non-sense CA in DsRed cells, due to the vesicular entrapment which is preventing the specifi c interaction between CA and cytosolic target. Since a comparable cellular distribution was visible for the enzyme targeted agent, a specifi c accumulation in -galactosidase containing cells is also unlikely. The results show that even though the designed CAs were effi ciently taken up into cells, they can interact specifi cally with the target only if colocalization is achieved. However, a lack of specifi city is caused by the endosomal entrapment. Further modifi cations are required to achieve the release from endosomes or a direct uptake into the cytosol.

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 Dates: 2008-10
 Publication Status: Published in print
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1002/psc.1090
BibTex Citekey: 5286
 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: P41815-047 Start / End Page: 154 - 155 Identifier: ISSN: 1075-2617
CoNE: https://pure.mpg.de/cone/journals/resource/954925604784