Document Detail

Metabolic cleavage and translocation efficiency of selected cell penetrating peptides: a comparative study with epithelial cell cultures.
MedLine Citation:
PMID:  18587651     Owner:  NLM     Status:  MEDLINE    
We investigated the metabolic stability of four cell penetrating peptides (CPPs), namely SAP, hCT(9-32)-br, [Palpha] and [Pbeta], when in contact with either subconfluent HeLa, confluent MDCK or Calu-3 epithelial cell cultures. Additionally, through analysis of their cellular translocation efficiency, we evaluated possible relations between metabolic stability and translocation efficiency. Metabolic degradation kinetics and resulting metabolites were assessed using RP-HPLC and MALDI-TOF mass spectrometry. Translocation efficiencies were determined using fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM). Between HeLa, MDCK and Calu-3 we found the levels of proteolytic activities to be highly variable. However, for each peptide, the individual degradation patterns were quite similar. The metabolic stability of the investigated CPPs was in the order of CF-SAP = CF-hCT(9-32)-br > [Pbeta]-IAF > [Palpha] and we identified specific cleavage sites for each of the four peptides. Throughout, we observed higher translocation efficiencies into HeLa cells as compared to MDCK and Calu-3, corresponding to the lower state of differentiation of HeLa cell cultures. No direct relation between metabolic stability and translocation efficiency was found, indicating that metabolic stability in general is not a main limiting factor for efficient cellular translocation. Nevertheless, translocation of individual CPPs may be improved by structural modifications aiming at increased metabolic stability.
Christina Foerg; Kathrin M Weller; Helene Rechsteiner; Hanne M Nielsen; Jimena Fernández-Carneado; René Brunisholz; Ernest Giralt; Hans P Merkle
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-28
Journal Detail:
Title:  The AAPS journal     Volume:  10     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-09-10     Completed Date:  2008-11-03     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  349-59     Citation Subset:  IM    
Institute of Pharmaceutical Sciences, ETH Zurich, Hönggerberg Campus, Wolfgang-Pauli-Strasse 10, CH-8093, Zurich, Switzerland.
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MeSH Terms
Amino Acid Sequence
Biological Transport
Cell Line
Cell Membrane Permeability*
Culture Media, Serum-Free
Drug Stability
Epithelial Cells* / drug effects,  metabolism
Flow Cytometry
Microscopy, Confocal
Molecular Sequence Data
Peptide Fragments* / administration & dosage,  chemistry,  metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/Peptide Fragments

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