The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells

Henriques, Sonia Troeira, Huang, Yen-Hua, Chaousis, Stephanie, Sani, Marc-Antoine, Poth, Aaron G., Separovic, Frances and Craik, David J. (2015) The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells. Chemistry and Biology, 22 8: 1087-1097. doi:10.1016/j.chembiol.2015.07.012

Author Henriques, Sonia Troeira
Huang, Yen-Hua
Chaousis, Stephanie
Sani, Marc-Antoine
Poth, Aaron G.
Separovic, Frances
Craik, David J.
Title The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells
Journal name Chemistry and Biology   Check publisher's open access policy
ISSN 1074-5521
Publication date 2015-08-20
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.chembiol.2015.07.012
Open Access Status Not Open Access
Volume 22
Issue 8
Start page 1087
End page 1097
Total pages 11
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2016
Language eng
Formatted abstract
Cyclotides combine the stability of disulfide-rich peptides with the intracellular accessibility of cell-penetrating peptides, giving them outstanding potential as drug scaffolds with an ability to inhibit intracellular protein-protein interactions. To realize and optimize the application of cyclotides as a drug framework and delivery system, we studied the ability of the prototypic cyclotide, kalata B1, to enter mammalian cells. We show that kalata B1 can enter cells via both endocytosis and direct membrane translocation. Both pathways are initiated by targeting phosphatidylethanolamine phospholipids at the cell surface and inducing membrane curvature. This unusual approach to initiate internalization might be harnessed to deliver drugs into cells and, in particular, cancer cells, which present a higher proportion of surface-exposed phosphatidylethanolamine phospholipids. Our findings highlight the potential of these peptides as drug leads for the modulation of traditionally “undruggable” targets, such as intracellular protein-protein interactions.
Keyword Cellular Uptake
Cyclic disulfide rich peptides
Lipid binding domains
Membrane translocation
Protein engineering
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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