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Intracellular targets: A multiple cargo transporting molecule
- Source :
- Journal of Peptide Science. 27
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- The generation of cell-penetrating peptides as cargo-delivery systems has produced an immense number of studies owing to the importance of these systems as tools to deliver molecules into the cells, as well as due to the interest to shed light into a yet unclear mechanism of the entrance of these peptides into the cells. However, many cell-penetrating peptides might present drawbacks due to causing cellular toxicity, or due to being entrapped in endosomes, or as a result of their degradation before they meet their target. In this work, a cargo transporting molecule, the Cell Penetrating Sequential Oligopeptide Carrier (CPSOC), formed by the repetitive -Lys-Aib-Cys- moiety, was tested for its ability to penetrate the cell membrane and transport the conjugated peptides into the cells. The cysteine residue anchors bioactive molecules through a stable thioether bond. The lysine supplies the positive charge to the construct, whereas the α-amino isobutyric acid is well known to induce helicoid conformation to the peptide backbone and protects from enzymatic degradation. The present study demonstrates that CPSOC penetrates the membrane transporting the conjugated cargo into the cell. When we tested CPSOC-conjugated peptides carrying critical domains of Cdc42, a small GTPase implicated in exocytosis, the internalized peptides were found to be functional because they inhibited exocytosis of von Willebrand factor from endothelial Weibel-Palade bodies a trafficking event depending on the Cdc42 protein. The data suggest that the carrier can deliver efficiently functional peptides into the cells, and thus, it can be used as a multiple-cargo transporting molecule.
- Subjects :
- Endosome
Cell-Penetrating Peptides
CDC42
010402 general chemistry
01 natural sciences
Biochemistry
Exocytosis
Cell membrane
Structural Biology
von Willebrand Factor
Drug Discovery
medicine
Small GTPase
Molecular Biology
Pharmacology
Oligopeptide
Weibel-Palade Bodies
010405 organic chemistry
Chemistry
Organic Chemistry
General Medicine
0104 chemical sciences
medicine.anatomical_structure
Membrane
Biophysics
Molecular Medicine
Intracellular
Subjects
Details
- ISSN :
- 10991387 and 10752617
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Peptide Science
- Accession number :
- edsair.doi.dedup.....a6c76ec714061877a59f4e5e12d2beb4