ArticleThe Biochemical journal2004
Metabolic cleavage of cell-penetrating peptides in contact with epithelial models: human calcitonin (hCT)-derived peptides, Tat(47-57) and penetratin(43-58).
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 74 citations in OpenAlex.
- Membrane-Traversing Peptides: Mechanistic Landscapes, Assays, and Applications.Chemical reviews · 2026Review
- Potential Enhancement of Topical Drug Delivery Using Grapefruit-derived Nanoparticles Modified Using TAT Peptide.Pharmaceutical research · 2026Article
- Antisense oligonucleotides: a novel Frontier in pharmacological strategy.Frontiers in pharmacology · 2023Review
- Elucidating the Therapeutic Potential of Cell-Penetrating Peptides in Human Tenon Fibroblast Cells.ACS omega · 2022Article
- Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System.Pharmaceutics · 2022Review
- In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Increased Carrier Peptide Stability through pH Adjustment Improves Insulin and PTH(1-34) Delivery In Vitro and In Vivo Rather than by Enforced Carrier Peptide-Cargo Complexation.Pharmaceutics · 2020Article
- A peptide for transcellular cargo delivery: Structure-function relationship and mechanism of action.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- CPP-E1A fusion peptides inhibit CtBP-mediated transcriptional repression.Molecular oncology · 2018Article
- Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos.International journal of molecular sciences · 2016Review
- PKA-type I selective constrained peptide disruptors of AKAP complexes.ACS chemical biology · 2015Article
- Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models.Cancer biology & therapy · 2014Article
- Cell-penetrating peptides as delivery vehicles for a protein-targeted terbium complex.Chemistry (Weinheim an der Bergstrasse, Germany) · 2012Article
- Cell-penetrating TAT peptide in drug delivery systems: proteolytic stability requirements.Drug delivery · 2011Article
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- TAT peptide and its conjugates: proteolytic stability.Bioconjugate chemistry · 2009Article
- Pharmacokinetic analysis of polyamide nucleic-acid-cell penetrating peptide conjugates targeted against HIV-1 transactivation response element.Oligonucleotides · 2008Article
- Metabolic cleavage and translocation efficiency of selected cell penetrating peptides: a comparative study with epithelial cell cultures.The AAPS journal · 2008Article
- Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives.Pharmaceutical research · 2007Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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