Detailed Analysis Concerning the Biodistribution and Metabolism of Human Calcitonin-Derived Cell-Penetrating Peptides

2008 ◽  
Vol 19 (8) ◽  
pp. 1596-1603 ◽  
Author(s):  
I. Neundorf ◽  
R. Rennert ◽  
J. Franke ◽  
I. Közle ◽  
R. Bergmann
Keyword(s):  
Detailed Analysis ◽  
Cell Penetrating Peptides ◽  
Human Calcitonin ◽  
Cell Penetrating

scholarly journals Metabolic cleavage of cell-penetrating peptides in contact with epithelial models: human calcitonin (hCT)-derived peptides, Tat(47–57) and penetratin(43–58)

2004 ◽  
Vol 382 (3) ◽  
pp. 945-956 ◽  
Author(s):  
Rachel TRÉHIN ◽  
Hanne M. NIELSEN ◽  
Heinz-Georg JAHNKE ◽  
Ulrike KRAUSS ◽  
Annette G. BECK-SICKINGER ◽  
...  
Keyword(s):  
Proteolytic Activity ◽  
Degradation Kinetics ◽  
Reversed Phase ◽  
Cell Penetrating Peptides ◽  
Human Calcitonin ◽  
Reversed Phase Hplc ◽  
Maldi Tof Ms ◽  
Cell Penetrating ◽  
Metabolic Degradation ◽  
Tof Ms

We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47–57) and penetratin(43–58), was through Fmoc (fluoren-9-ylmethoxycarbonyl) chemistry. Metabolic degradation kinetics of the tested CPP in contact with three cell-cultured epithelial models, MDCK (Madin–Darby canine kidney), Calu-3 and TR146, was evaluated by reversed-phase HPLC. Identification of the resulting metabolites of CF-hCT(9–32) was through reversed-phase HPLC fractionation and peak allocation by MALDI–TOF-MS (matrix-assisted laser-desorption ionization–time-of-flight mass spectrometry) or direct MALDI–TOF-MS of incubates. Levels of proteolytic activity varied highly between the investigated epithelial models and the CPP. The Calu-3 model exhibited the highest proteolytic activity. The patterns of metabolic cleavage of hCT(9–32) were similar in all three models. Initial cleavage of this peptide occurred at the N-terminal domain, possibly by endopeptidase activity yielding both the N- and the C-terminal counterparts. Further metabolic degradation was by aminopeptidase, endopeptidase and/or carboxypeptidase activities. In conclusion, when in contact with epithelial models, the studied CPP were subject to efficient metabolism, a prerequisite of cargo release on the one hand, but with potential for premature cleavage and loss of the cargo as well on the other. The results, particularly on hCT(9–32), may be used as a template to suggest structural modifications towards improved CPP performance.

scholarly journals Membrane Surface-Associated Helices Promote Lipid Interactions and Cellular Uptake of Human Calcitonin-Derived Cell Penetrating Peptides

2005 ◽  
Vol 89 (6) ◽  
pp. 4056-4066 ◽  
Author(s):  
Michael E. Herbig ◽  
Kathrin Weller ◽  
Ulrike Krauss ◽  
Annette G. Beck-Sickinger ◽  
Hans P. Merkle ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Membrane Surface ◽  
Cell Penetrating Peptides ◽  
Human Calcitonin ◽  
Lipid Interactions ◽  
Cell Penetrating

scholarly journals Cellular Uptake But Low Permeation of Human Calcitonin-Derived Cell Penetrating Peptides and Tat(47-57) Through Well-Differentiated Epithelial Models

2004 ◽  
Vol 21 (7) ◽  
pp. 1248-1256 ◽  
Author(s):  
Rachel Tréhin ◽  
Ulrike Krauss ◽  
Annette G. Beck-Sickinger ◽  
Hans P. Merkle ◽  
Hanne M. Nielsen
Keyword(s):  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Human Calcitonin ◽  
Cell Penetrating ◽  
Well Differentiated
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