Retro-inversion of certain cell-penetrating peptides causes severe cellular toxicity
2011 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1808, no 6, 1544-1551 p.Article in journal (Refereed) Published
Cell-penetrating peptides (CPPs) are a promising group of delivery vectors for various therapeutic agents but their application is often hampered by poor stability in the presence of serum. Different strategies to improve peptide stability have been exploited, one of them being "retro-inversion" (RI) of natural peptides. With this approach the stability of CPPs has been increased, thereby making them more efficient transporters. Several RI-CPPs were here assessed and compared to the corresponding parent peptides in different cell-lines. Surprisingly, treatment of cells with these peptides induced trypsin insensitivity and rapid severe toxicity in contrast to l-peptides. This was measured as reduced metabolic activity and condensed cell nuclei, in parity with the apoptosis inducing agent staurosporine. Furthermore, effects on mitochondrial network, focal adhesions, actin cytoskeleton and caspase-3 activation were analyzed and adverse effects were evident at 20μM peptide concentration within 4h while parent l-peptides had negligible effects. To our knowledge this is the first time RI peptides are reported to cause cellular toxicity, displayed by decreased metabolic activity, morphological changes and induction of apoptosis. Considering the wide range of research areas that involves the use of RI-peptides, this finding is of major importance and needs to be taken under consideration in applications of RI-peptides.
Place, publisher, year, edition, pages
2011. Vol. 1808, no 6, 1544-1551 p.
Cell-penetrating peptide, Retro-inverso, Cytotoxicity, Hydrophobicity, Apoptosis
IdentifiersURN: urn:nbn:se:su:diva-52312DOI: 10.1016/j.bbamem.2010.10.019ISI: 000290705700014PubMedID: 21070744OAI: oai:DiVA.org:su-52312DiVA: diva2:387018
authorCount :72011-01-132011-01-132015-04-21Bibliographically approved