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Targeted Subcellular Protein Delivery Using Cleavable Cyclic Cell-Penetrating Peptide-Conjugates

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Specialty Molecular Biology
Date 2021 Aug 13
PMID 34386966
Citations 1
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Abstract

Proteins conjugated to cyclic cell-penetrating peptides (cCPPs) haAbstractve been shown to be effectively taken up by living cells. Conjugation of proteins to cCPPs in a cleavable manner leads to localization in the cytosol and immediate bioavailability of the protein after uptake. Here we describe how mCherry, a fluorescent protein, can be targeted to a membrane-bound compartment, the nucleus, and a subcellular structure like the actin cytoskeleton after cCPP-mediated uptake into living cells. Targeting peptides are genetically fused to the mCherry protein sequence and the protein is conjugated to the cCPP via a cleavable disulfide bond. Localization of mCherry in the nucleus or the actin skeleton respectively can be observed by live cell confocal fluorescence microscopy.

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References
1.
Fu A, Tang R, Hardie J, Farkas M, Rotello V . Promises and pitfalls of intracellular delivery of proteins. Bioconjug Chem. 2014; 25(9):1602-8. PMC: 4166028. DOI: 10.1021/bc500320j. View

2.
Pei D, Buyanova M . Overcoming Endosomal Entrapment in Drug Delivery. Bioconjug Chem. 2018; 30(2):273-283. PMC: 6501178. DOI: 10.1021/acs.bioconjchem.8b00778. View

3.
Cronican J, Thompson D, Beier K, McNaughton B, Cepko C, Liu D . Potent delivery of functional proteins into Mammalian cells in vitro and in vivo using a supercharged protein. ACS Chem Biol. 2010; 5(8):747-52. PMC: 2924640. DOI: 10.1021/cb1001153. View

4.
Fuchs S, Raines R . Arginine grafting to endow cell permeability. ACS Chem Biol. 2007; 2(3):167-70. PMC: 2813566. DOI: 10.1021/cb600429k. View

5.
Zelphati O, Wang Y, Kitada S, Reed J, Felgner P, Corbeil J . Intracellular delivery of proteins with a new lipid-mediated delivery system. J Biol Chem. 2001; 276(37):35103-10. DOI: 10.1074/jbc.M104920200. View