English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Novel Cysteine-rich Cell Penetrating Peptide: Efficient Uptake and Cytosolic Localization

Jha, D., Mishra, R., Ugurbil, K., Engelmann, J., & Wiesmüller, K.-H. (2008). Novel Cysteine-rich Cell Penetrating Peptide: Efficient Uptake and Cytosolic Localization. Poster presented at 30th European Peptide Symposium (30 EPS), Helsinki, Finland.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-C773-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-8B94-9
Genre: Poster

Files

show Files

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Jha, D1, 2, Author              
Mishra, R1, 2, Author              
Ugurbil, K, Author
Engelmann, J1, 2, Author              
Wiesmüller, K-H, Author
Affiliations:
1Former Department MRZ, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528700              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

Content

show
hide
Free keywords: -
 Abstract: Introduction: Crossing the plasma membrane is a prerequisite for intracellular targeted drug delivery. Cell penetrating peptides are actively used as the delivery tool for intracellular delivery of various cargos. However, confinement of biomolecules into endosomes limits their use for intracellular targeting. Therefore, there is a need for vectors capable of transferring cargo molecules directly into the cytoplasm. Herein, we focus on the development of a novel CPP (derived from polypeptide Crotamine [1]) which shows an efficient uptake at low concentrations (amp;amp;amp;8804;2.5 amp;amp;amp;956;M) and cytosolic distribution along with vesicular uptake. Methods: Series of peptides were synthesized by Fmoc strategy, introducing mutations in Cro (27-39) (proposed CPP sequence in Crotamine). All were N-terminally labeled with fluorescein isothiocyanate for optical imaging. Structure Activity Relationship (SAR) studies were done by substitution and/or deletion of amino acid residues in the sequence observing the uptake behaviour by fluorescence spectroscopy and microscopy. Results: Amongst 60 synthesized peptides, one of shorter length showed the best intracellular delivery and cytosolic distribution at lower concentration (2.5 amp;amp;amp;956;M) when compared to other CPP. Replacing or deleting cysteines had negative impact on internalization. Results also displayed the involvement of tryptophans in cellular uptake indicating, along with cationic amino acids, the importance of each residue in this optimized sequence. Conclusions: SAR studies identified a novel cell penetrating peptide showing, besides of endosomal uptake, also an efficient delivery into the cytoplasm at low concentrations. Thus, this peptide might prove useful for efficient transmembrane delivery of agents directed to cytosolic targets.

Details

show
hide
Language(s):
 Dates: 2008-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1002/psc.1090
BibTex Citekey: 5351
 Degree: -

Event

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

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Peptide Science
  Other : J. Peptide Sci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Chichester, West Sussex, UK : John Wiley & Sons
Pages: - Volume / Issue: 14 (Supplement 1) Sequence Number: P41915-055 Start / End Page: 157 Identifier: ISSN: 1075-2617
CoNE: https://pure.mpg.de/cone/journals/resource/954925604784