The agony of choice: how to find a suitable CPP for cargo delivery

Autor: Julia Triebus, Rudolf Volkmer, Judith Müller, Ines Kretzschmar, Prisca Boisguerin
Rok vydání: 2012
Předmět:
Zdroj: Journal of Peptide Science. 18:293-301
ISSN: 1075-2617
DOI: 10.1002/psc.2396
Popis: Successful and effective cellular delivery remains a main obstacles in the medical field. The use of cell-penetrating peptides (CPPs) has become one of the most important tools for the internalisation of a wide range of molecules including pharmaceuticals. It is still difficult to choose one CPP for one biological application because there is no ubiquitous CPP meeting the diverse requirements. In our case, we are looking for a suitable CPP to deliver the pro-apoptotic KLA peptide (KLAKLAKKLAKLAK) by a simple co-incubation strategy. For that reason, we selected three different cell lines (fibroblastic, cancerous and macrophagic cells) and studied the uptake and subcellular localisation of six different CPPs alone as well as mixed with the KLA peptide. Furthermore, we used the CPPs with a carboxyamidated or a carboxylated C-terminus and analysed the impact of the C-termini on internalisation and cargo delivery. We could clearly showed that the cellular CPP uptake is not only dependent on the used CPP and cell line but also highly affected by its chemical nature of the C-terminus (uptake: carboxyamidated CPPs > carboxylated CPPs) and can influence its cellular localisation. We successfully delivered the KLA peptide in the three cell lines and learned that here as well, the C-terminus is crucial for an effective peptide delivery. Finally, we induced apoptosis in mouse leukaemic monocyte macrophage (RAW 264.7) and in human breast adenocarcinoma (MCF-7) cells using the mixture of amidated MPG peptide : KLA and in african green monkey kidney fibroblast (Cos-7) cells using carboxylated integrin peptide : KLA. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Databáze: OpenAIRE
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