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Open AccessArticle

Fusion of a Short HA2-Derived Peptide Sequence to Cell-Penetrating Peptides Improves Cytosolic Uptake, but Enhances Cytotoxic Activity

1
Institut für Biochemie; Fakultät für Biowissenschaften, Pharmazie und Psychologie; Universität Leipzig, Brüderstr. 34, D-04103 Leipzig, Germany
2
Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimerfeld 364, D-69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally to the paper.
Pharmaceuticals 2009, 2(2), 49-65; https://doi.org/10.3390/ph2020049
Received: 10 August 2009 / Revised: 22 September 2009 / Accepted: 24 September 2009 / Published: 25 September 2009
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
Cell-penetrating peptides (CPP) have become a widely used tool for efficient cargo delivery into cells. However, one limiting fact is their uptake by endocytosis causing the enclosure of the CPP-cargo construct within endosomes. One often used method to enhance the outflow into the cytosol is the fusion of endosome-disruptive peptide or protein sequences to CPP. But, until now, no studies exist investigating the effects of the fusion peptide to the cellular distribution, structural arrangements and cytotoxic behaviour of the CPP. In this study, we attached a short modified sequence of hemagglutinin subunit HA2 to different CPP and analysed the biologic activity of the new designed peptides. Interestingly, we observed an increased cytosolic distribution but also highly toxic activities in the micromolar range against several cell lines. Structural analysis revealed that attachment of the fusion peptide had profound implications on the whole conformation of the peptide, which might be responsible for membrane interaction and endosome disruption. View Full-Text
Keywords: membrane fusion; hemagglutinin; cell-penetrating peptides; CAP18; cytotoxicity; drug delivery membrane fusion; hemagglutinin; cell-penetrating peptides; CAP18; cytotoxicity; drug delivery
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MDPI and ACS Style

Neundorf, I.; Rennert, R.; Hoyer, J.; Schramm, F.; Löbner, K.; Kitanovic, I.; Wölfl, S. Fusion of a Short HA2-Derived Peptide Sequence to Cell-Penetrating Peptides Improves Cytosolic Uptake, but Enhances Cytotoxic Activity. Pharmaceuticals 2009, 2, 49-65.

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