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Issue 1, 2015
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Delivery of mirror image polypeptides into cells

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Abstract

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

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Publication details

The article was received on 14 Jul 2014, accepted on 09 Sep 2014 and first published on 25 Sep 2014


Article type: Edge Article
DOI: 10.1039/C4SC02078B
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Chem. Sci., 2015,6, 648-653
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    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

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