A chemical toolkit for proteins — an expanded genetic code

Abstract

Recently, a method to encode unnatural amino acids with diverse physicochemical and biological properties genetically in bacteria, yeast and mammalian cells was developed. Over 30 unnatural amino acids have been co-translationally incorporated into proteins with high fidelity and efficiency using a unique codon and corresponding transfer-RNA:aminoacyl–tRNA-synthetase pair. This provides a powerful tool for exploring protein structure and function in vitro and in vivo, and for generating proteins with new or enhanced properties.

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Figure 1: Encoding unnatural amino acids in prokaryotes.
Figure 2: Unnatural amino acids that have been added to the genetic codes of prokaryotes and eukaryotes.
Figure 3: The site-specific incorporation of a coumarin-derived fluorescent amino acid into myoglobin as a probe of protein conformational changes.
Figure 4: The structures of the wild-type and a mutant Methanococcus jannaschii tyrosyl–tRNA synthetase bound to their cognate amino acids.

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Acknowledgements

Work in the laboratory of P.G.S. is supported by the National Institutes of Health, the United States Department of Energy and the Skaggs Institute for Chemical Biology.

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Xie, J., Schultz, P. A chemical toolkit for proteins — an expanded genetic code. Nat Rev Mol Cell Biol 7, 775–782 (2006). https://doi.org/10.1038/nrm2005

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