Publication: Rational design of a series of novel amphipathic cell-penetrating peptides
Issued Date
2014-04-10
Resource Type
ISSN
18733476
03785173
03785173
Other identifier(s)
2-s2.0-84896736402
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Pharmaceutics. Vol.464, No.1-2 (2014), 111-116
Suggested Citation
Jakob Regberg, Artita Srimanee, Mikael Erlandsson, Rannar Sillard, Dimitar A. Dobchev, Mati Karelson, Ülo Langel Rational design of a series of novel amphipathic cell-penetrating peptides. International Journal of Pharmaceutics. Vol.464, No.1-2 (2014), 111-116. doi:10.1016/j.ijpharm.2014.01.018 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34904
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Rational design of a series of novel amphipathic cell-penetrating peptides
Other Contributor(s)
Abstract
A series of novel, amphipathic cell-penetrating peptides was developed based on a combination of the model amphipathic peptide sequence and modifications based on the strategies developed for PepFect and NickFect peptides. The aim was to study the role of amphipathicity for peptide uptake and to investigate if the modifications developed for PepFect peptides could be used to improve the uptake of another class of cell-penetrating peptides. The peptides were synthesized by solid phase peptide synthesis and characterized by circular dichroism spectroscopy. Non-covalent peptide-plasmid complexes were formed by co-incubation of the peptides and plasmids in water solution. The complexes were characterized by dynamic light scattering and cellular uptake of the complexes was studied in a luciferase-based plasmid transfection assay. A quantitative structure-activity relationship (QSAR) model of cellular uptake was developed using descriptors including hydrogen bonding, peptide charge and positions of nitrogen atoms. The peptides were found to be non-toxic and could efficiently transfect cells with plasmid DNA. Cellular uptake data was correlated to QSAR predictions and the predicted biological effects obtained from the model correlated well with experimental data. The QSAR model could improve the understanding of structural requirements for cell penetration, or could potentially be used to predict more efficient cell-penetrating peptides. © 2014 Elsevier B.V.