Journal ArticleDOI
An Expanded Eukaryotic Genetic Code
Jason W. Chin,T. Ashton Cropp,J. Christopher Anderson,Mridul Mukherji,Zhiwen Zhang,Peter G. Schultz +5 more
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TLDR
A general and rapid route for the addition of unnatural amino acids to the genetic code of Saccharomyces cerevisiae is described, providing a gateway to the systematic expansion of the genetic codes of multicellular eukaryotes.Abstract:
We describe a general and rapid route for the addition of unnatural amino acids to the genetic code of Saccharomyces cerevisiae. Five amino acids have been incorporated into proteins efficiently and with high fidelity in response to the nonsense codon TAG. The side chains of these amino acids contain a keto group, which can be uniquely modified in vitro and in vivo with a wide range of chemical probes and reagents; a heavy atom-containing amino acid for structural studies; and photocrosslinkers for cellular studies of protein interactions. This methodology not only removes the constraints imposed by the genetic code on our ability to manipulate protein structure and function in yeast, it provides a gateway to the systematic expansion of the genetic codes of multicellular eukaryotes.read more
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Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality
TL;DR: The bioorthogonal chemical reactions developed to date are described and how they can be used to study biomolecules.
Journal ArticleDOI
Water as an Active Constituent in Cell Biology
TL;DR: The recent confirmation that there is at least one world rich in organic molecules on which rivers and perhaps shallow seas or bogs are filled with nonaqueous fluidsthe liquid hydrocarbons of Titan now bring some focus, even urgency, to the question of whether water is indeed a matrix of life.
Journal ArticleDOI
Copper-free click chemistry for dynamic in vivo imaging
Jeremy M. Baskin,Jennifer A. Prescher,Scott T. Laughlin,Nicholas J. Agard,Pamela V. Chang,Isaac A. Miller,Anderson Lo,Julian A. Codelli,Carolyn R. Bertozzi +8 more
TL;DR: A Cu-free variant of click chemistry that can label biomolecules rapidly and selectively in living systems, overcoming the intrinsic toxicity of the canonical Cu-catalyzed reaction is reported.
Journal ArticleDOI
Adding New Chemistries to the Genetic Code
Chang C. Liu,Peter G. Schultz +1 more
TL;DR: The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addition of approximately 70 unnatural amino acids to the genetic codes of Escherichia coli, yeast, and mammalian cells, which provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function.
Journal ArticleDOI
Chemistry in living systems.
TL;DR: This review highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems.
References
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Journal ArticleDOI
A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance.
TL;DR: Mutations at the URA3 locus of Saccharomyces cerevisiae can be obtained by a positive selection, based on the loss of orotidine-5′-phosphate decarboxylase activity, and seems applicable to a variety of eucaryotic and procaryotic cells.
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Expanding the Genetic Code of Escherichia coli
TL;DR: A unique transfer RNA/aminoacyl-tRNA synthetase pair has been generated that expands the number of genetically encoded amino acids in Escherichia coli and should provide a general method for increasing the genetic repertoire of living cells to include a variety of amino acids with novel structural, chemical, and physical properties not found in the common 20 amino acids.
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Solid phase synthesis
TL;DR: The purpose today is to describe the chemical synthesis of peptides and proteins and to discuss the use of the synthetic approach to answer various biological questions.
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A general method for site-specific incorporation of unnatural amino acids into proteins.
TL;DR: The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function.
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Synthesis of native proteins by chemical ligation.
TL;DR: The facile access to novel analogs provided by chemical protein synthesis has led to original insights into the molecular basis of protein function in a number of systems.