2. Academic Validation
  3. The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells

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

  • Chem Biol. 2015 Aug 20;22(8):1087-97. doi: 10.1016/j.chembiol.2015.07.012.
Sónia Troeira Henriques 1,  Yen-Hua Huang 2,  Stephanie Chaousis 2,  Marc-Antoine Sani 3,  Aaron G Poth 2,  Frances Separovic 3,  David J Craik 4
Affiliations

Affiliations

  • 1 Institute for Molecular Bioscience, Chemical and Structural Biology Division, The University of Queensland, Brisbane, 4072 QLD, Australia. Electronic address: s.henriques@uq.edu.au.
  • 2 Institute for Molecular Bioscience, Chemical and Structural Biology Division, The University of Queensland, Brisbane, 4072 QLD, Australia.
  • 3 School of Chemistry, Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, 3010 VIC, Australia.
  • 4 Institute for Molecular Bioscience, Chemical and Structural Biology Division, The University of Queensland, Brisbane, 4072 QLD, Australia. Electronic address: d.craik@imb.uq.edu.au.
PMID: 26278183 DOI: 10.1016/j.chembiol.2015.07.012
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.

Keywords

cellular uptake; cyclic disulfide-rich peptides; lipid-binding domains; membrane translocation; protein engineering.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z