Issue 12, 2016

A genetically encoded multifunctional unnatural amino acid for versatile protein manipulations in living cells

Abstract

The genetic code expansion strategy allowed incorporation of unnatural amino acids (UAAs) bearing diverse functional groups into proteins, providing a powerful toolkit for protein manipulation in living cells. We report a multifunctional UAA, Nε-p-azidobenzyloxycarbonyl lysine (PABK), that possesses a panel of unique properties capable of fulfilling various protein manipulation purposes. In addition to being used as a bioorthogonal ligation handle, an infrared probe and a photo-affinity reagent, PABK was shown to be chemically decaged by trans-cyclooctenols via a strain-promoted 1,3-dipolar cycloaddition, which provides a new bioorthogonal cleavage strategy for intracellular protein activation. The biocompatibility and efficiency of this method were demonstrated by decaging of a PABK-caged firefly luciferase under living conditions. We further extended this method to chemically rescue a bacterial toxin OspF inside mammalian host cells.

Graphical abstract: A genetically encoded multifunctional unnatural amino acid for versatile protein manipulations in living cells

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Jun 2016
Accepted
01 Aug 2016
First published
01 Aug 2016
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., 2016,7, 7055-7060

A genetically encoded multifunctional unnatural amino acid for versatile protein manipulations in living cells

Y. Ge, X. Fan and P. R. Chen, Chem. Sci., 2016, 7, 7055 DOI: 10.1039/C6SC02615J

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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