Issue 12, 2018

Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation

Abstract

We have developed a general peptide macrocyclization strategy that involves a facile and chemoselective methionine bis-alkylation/dealkylation process. This method provides a straightforward and easy approach to generate cyclic peptides with tolerances of all amino acids (including Cys), variable loop sizes, and different linkers. The Met bis-alkylation we apply in this strategy yields two additional on-tether positive charges that could assist in the cellular uptake of the peptides. Notably, the bis-alkylated peptide could be reduced to release the original peptide both in vitro and within cellular environments. This strategy provides an intriguing and facile traceless post-peptide-synthesis modification with enhanced cellular uptakes. Peptides constructed with this method could be utilized to zero in on various protein targets or to achieve other goals, such as drug delivery.

Graphical abstract: Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation

Supplementary files

Article information

Article type
Edge Article
Submitted
30 Nov 2017
Accepted
20 Feb 2018
First published
26 Feb 2018
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., 2018,9, 3227-3232

Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation

X. Shi, R. Zhao, Y. Jiang, H. Zhao, Y. Tian, Y. Jiang, J. Li, W. Qin, F. Yin and Z. Li, Chem. Sci., 2018, 9, 3227 DOI: 10.1039/C7SC05109C

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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