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Tytuł pozycji:

Delivery of mirror image polypeptides into cells.

Tytuł:
Delivery of mirror image polypeptides into cells.
Autorzy:
Rabideau AE; Department of Chemistry , Massachusetts Institute of Technology , 77 Massachusetts Ave. 18-596 , Cambridge , MA 02139 , USA . Email: .
Liao X; Department of Chemistry , Massachusetts Institute of Technology , 77 Massachusetts Ave. 18-596 , Cambridge , MA 02139 , USA . Email: .
Pentelute BL; Department of Chemistry , Massachusetts Institute of Technology , 77 Massachusetts Ave. 18-596 , Cambridge , MA 02139 , USA . Email: .
Źródło:
Chemical science [Chem Sci] 2015 Jan 01; Vol. 6 (1), pp. 648-653. Date of Electronic Publication: 2014 Sep 25.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Cambridge, UK : Royal Society of Chemistry, [2010]-
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Grant Information:
U54 AI057159 United States AI NIAID NIH HHS
Entry Date(s):
Date Created: 20170715 Latest Revision: 20201001
Update Code:
20240105
PubMed Central ID:
PMC5492103
DOI:
10.1039/c4sc02078b
PMID:
28706631
Czasopismo naukowe
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, LF N . 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 LF N 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/LF N system is adaptable for the intracellular delivery of mirror image peptides and proteins.

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