Issue 11, 2017

Achieving enhanced cell penetration of short conformationally constrained peptides through amphiphilicity tuning

Abstract

Due to their enhanced stability and cell permeability, cyclic cell-penetrating peptides have been widely used as delivery vectors for transporting cell-impermeable cargos into cells. In this study, we synthesized a panel of conformationally constrained peptides with either α-helix or β-hairpin conformations. We tuned the amphiphilicity of these constrained peptides with different distributions of charged or hydrophobic residues and compared their cellular uptake efficiencies in different cell lines. We found that the amphipathicity of these conformationally constrained peptides correlates well with their cellular uptake efficiency. We proposed that peptides with larger hydrophobic moments (HMs) have stronger binding affinities with the cell membrane which further accelerates the endocytosis process. This finding should provide an approach towards the design of more potent conformationally constrained cell-penetrating peptides for biomedical applications.

Graphical abstract: Achieving enhanced cell penetration of short conformationally constrained peptides through amphiphilicity tuning

Supplementary files

Article information

Article type
Edge Article
Submitted
17 Aug 2017
Accepted
12 Sep 2017
First published
13 Sep 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 7576-7581

Achieving enhanced cell penetration of short conformationally constrained peptides through amphiphilicity tuning

Y. Tian, X. Zeng, J. Li, Y. Jiang, H. Zhao, D. Wang, X. Huang and Z. Li, Chem. Sci., 2017, 8, 7576 DOI: 10.1039/C7SC03614K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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