Next Article in Journal
Hypertensive Emergency in Aortic Dissection and Thoracic Aortic Aneurysm—A Review of Management
Next Article in Special Issue
Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide
Previous Article in Journal
Antihypertensive Drug and Inner Ear Perfusion: An Otologist’s Point of View
Article Menu

Export Article

Open AccessArticle
Pharmaceuticals 2009, 2(2), 49-65; doi:10.3390/ph2020049

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
Authors contributed equally to the paper.
*
Author to whom correspondence should be addressed.
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)

Abstract

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.
Keywords: membrane fusion; hemagglutinin; cell-penetrating peptides; CAP18; cytotoxicity; drug delivery membrane fusion; hemagglutinin; cell-penetrating peptides; CAP18; cytotoxicity; drug delivery
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top