Issue 1, 2015

Delivery of mirror image polypeptides into cells


Mirror image peptides have unique stability and immunogenic properties in mammals, making them attractive agents to investigate. Their properties inside cells have been mostly unexplored because biopolymers are difficult to transport across cellular membranes. Here, we used protective antigen (PA) from anthrax toxin to deliver mirror image polypeptide cargo into the cytosol of mammalian cells when conjugated to the C-terminus of the PA-binding domain of lethal factor, LFN. We found mirror image polypeptides and proteins were translocated as efficiently into cells as their L counterparts. Once in the cytosol, by the use of western blot, we found that D peptides at the C-terminus of LFN were able to achieve higher steady state concentrations when compared to the L-peptide conjugate. With this platform, we delivered a D-peptide MDM2 antagonist to disrupt the p53/MDM2 interaction in cancer cells. For the first time, we show the PA/LFN system is adaptable for the intracellular delivery of mirror image peptides and proteins.

Graphical abstract: Delivery of mirror image polypeptides into cells

Supplementary files

Article information

Article type
Edge Article
14 Jul 2014
09 Sep 2014
First published
25 Sep 2014
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2015,6, 648-653

Author version available

Delivery of mirror image polypeptides into cells

A. E. Rabideau, X. Liao and B. L. Pentelute, Chem. Sci., 2015, 6, 648 DOI: 10.1039/C4SC02078B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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