uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone: Effects of hydrogen bonding and alpha-chirality in the beta-peptoid residues
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Show others and affiliations
2012 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1818, no 11, 2660-2668 p.Article in journal (Refereed) Published
Abstract [en]

Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone were studied to evaluate the effect of alpha-chirality in the beta-peptoid residues and the presence of guanidinium groups in the alpha-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were studied along with their adsorption to lipid bilayers, cellular uptake, and toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected their adsorbed amounts onto lipid bilayers as well as with their cellular uptake, indicating the importance of hydrogen bonding for their membrane interaction and cellular uptake. Ellipsometry studies further demonstrated that the presence of chiral centers in the beta-peptoid residues promotes a higher adsorption to anionic lipid bilayers, whereas circular dichroism results showed that alpha-chirality influences their overall mean residue ellipticity. The presence of guanidinium groups and alpha-chiral beta-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells.

Place, publisher, year, edition, pages
2012. Vol. 1818, no 11, 2660-2668 p.
Keyword [en]
Chirality, Hydrogen bonding, Cell-penetrating peptide, Peptidomimetic, Adsorption, Binding constant
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-183534DOI: 10.1016/j.bbamem.2012.05.003ISI: 000309081700020OAI: oai:DiVA.org:uu-183534DiVA: diva2:575165
Available from: 2012-12-07 Created: 2012-10-29 Last updated: 2012-12-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Malmsten, Martin
By organisation
Department of Pharmacy
In the same journal
Biochimica et Biophysica Acta - Biomembranes
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 142 hits
ReferencesLink to record
Permanent link

Direct link