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- Title
Covalent Attachment of Cyclic TAT Peptides to GFP Results in Protein Delivery into Live Cells with Immediate Bioavailability.
- Authors
Nischan, Nicole; Hackenberger, Christian P. R.; Natale, Francesco; Cardoso, M. Cristina; Herce, Henry D.; Bohlke, Nina; Budisa, Nediljko
- Abstract
The delivery of free molecules into the cytoplasm and nucleus by using arginine-rich cell-penetrating peptides (CPPs) has been limited to small cargoes, while large cargoes such as proteins are taken up and trapped in endocytic vesicles. Based on recent work, in which we showed that the transduction efficiency of arginine-rich CPPs can be greatly enhanced by cyclization, the aim was to use cyclic CPPs to transport full-length proteins, in this study green fluorescent protein (GFP), into the cytosol of living cells. Cyclic and linear CPP-GFP conjugates were obtained by using azido-functionalized CPPs and an alkyne-functionalized GFP. Our findings reveal that the cyclic-CPP-GFP conjugates are internalized into live cells with immediate bioavailability in the cytosol and the nucleus, whereas linear CPP analogues do not confer GFP transduction. This technology expands the application of cyclic CPPs to the efficient transport of functional full-length proteins into live cells.
- Subjects
CYCLIC peptides; GREEN fluorescent protein; BIOAVAILABILITY; CELL-penetrating peptides; FREE molecules; CYTOPLASM; CELL nuclei; RING formation (Chemistry)
- Publication
Angewandte Chemie International Edition, 2015, Vol 54, Issue 6, p1950
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201410006