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Issue 11, 2015
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Illuminating biological processes through site-specific protein labeling

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Coupling genetically encoded peptide tags or unnatural amino acids (UAAs) with bioorthogonal reactions allows for precise control over the protein-labeling sites as well as the wide choice of labeling dyes. However, the value of these site-specific protein labeling strategies in a real biology setting, particularly their advantages over conventional labeling methods including fluorescent proteins (FPs), remains to be fully demonstrated. In this tutorial review, we first introduce various strategies for site-specific protein labeling that utilize artificial peptide sequences or genetically encoded UAAs as the labeling handle. Emphasis will be placed on introducing the advantages of protein site-specific labeling techniques as well as their applications in solving biological problems, particularly as to why a site-specific protein labeling approach is needed. Finally, beyond the widely used single site-specific labeling methods, the recently emerged dual site-specific protein labeling strategies will be introduced together with their fast-growing potential in illustrating biological processes.

Graphical abstract: Illuminating biological processes through site-specific protein labeling

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Article information

17 Nov 2014
First published
10 Apr 2015

Chem. Soc. Rev., 2015,44, 3405-3417
Article type
Tutorial Review

Illuminating biological processes through site-specific protein labeling

G. Zhang, S. Zheng, H. Liu and P. R. Chen, Chem. Soc. Rev., 2015, 44, 3405
DOI: 10.1039/C4CS00393D

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