A chemical toolkit for proteins — an expanded genetic code

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.

[1]  P G Schultz,et al.  Expanding the Genetic Code of Escherichia coli , 2001, Science.

[2]  B. Erlanger,et al.  Photochromic activators of the acetylcholine receptor. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Schultz,et al.  Structural characterization of a p-acetylphenylalanyl aminoacyl-tRNA synthetase. , 2005, Journal of the American Chemical Society.

[4]  Peter G Schultz,et al.  An expanded genetic code with a functional quadruplet codon. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  O. Siddiqi,et al.  Suppression of mutations in the alkaline phosphatase structural cistron of E. coli. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Chin,et al.  Photo-cross-linking interacting proteins with a genetically encoded benzophenone , 2005, Nature Methods.

[7]  Probing Protein Structure and Function with an Expanded Genetic Code , 1995 .

[8]  S. Altman,et al.  Context effects on nonsense codon suppression in Escherichia coli. , 1978, Genetics.

[9]  C. Glabe,et al.  Biosynthetic site-specific incorporation of a non-natural amino acid into a polypeptide , 1989 .

[10]  A. Böck,et al.  Selenocysteine: the 21st amino acid , 1991, Molecular microbiology.

[11]  Brian A. Smith,et al.  A new strategy for the site-specific modification of proteins in vivo. , 2003, Biochemistry.

[12]  Peter G Schultz,et al.  A genetically encoded photocaged tyrosine. , 2006, Angewandte Chemie.

[13]  Peter G Schultz,et al.  A genetically encoded fluorescent amino acid. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Schultz,et al.  Adding amino acids with novel reactivity to the genetic code of Saccharomyces cerevisiae. , 2003, Journal of the American Chemical Society.

[15]  P. Schultz,et al.  In Vivo Photocrosslinking with Unnatural Amino Acid Mutagenesis , 2002, Chembiochem : a European journal of chemical biology.

[16]  P. Ascenzi,et al.  Unfolding of the loggerhead sea turtle (Caretta caretta) myoglobin: A 1H‐NMR and electronic absorbance study , 2002, Protein science : a publication of the Protein Society.

[17]  E. Goldman,et al.  Editing of errors in selection of amino acids for protein synthesis. , 1992, Microbiological reviews.

[18]  K. Kirshenbaum,et al.  Biosynthesis of Proteins Incorporating a Versatile Set of Phenylalanine Analogues. , 2002 .

[19]  Wei Lu,et al.  Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. , 2001, Molecular cell.

[20]  W. DeGrado,et al.  p-Benzoyl-L-phenylalanine, a new photoreactive amino acid. Photolabeling of calmodulin with a synthetic calmodulin-binding peptide. , 1986, The Journal of biological chemistry.

[21]  G. Hortin,et al.  Applications of amino acid analogs for studying co- and posttranslational modifications of proteins. , 1983, Methods in enzymology.

[22]  Andrew B. Martin,et al.  Addition of a photocrosslinking amino acid to the genetic code of Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Andrew B. Martin,et al.  Generation of a bacterium with a 21 amino acid genetic code. , 2003, Journal of the American Chemical Society.

[24]  Peter G Schultz,et al.  An Expanded Eukaryotic Genetic Code , 2003, Science.

[25]  Bernd Bukau,et al.  Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB , 2004, Cell.

[26]  P. Schultz,et al.  An archaebacteria-derived glutamyl-tRNA synthetase and tRNA pair for unnatural amino acid mutagenesis of proteins in Escherichia coli. , 2003, Nucleic acids research.

[27]  Andrew B. Martin,et al.  Addition of p-azido-L-phenylalanine to the genetic code of Escherichia coli. , 2002, Journal of the American Chemical Society.

[28]  Peter G Schultz,et al.  A genetically encoded photocaged amino acid. , 2004, Journal of the American Chemical Society.

[29]  Joseph A. Krzycki,et al.  Pyrrolysine Encoded by UAG in Archaea: Charging of a UAG-Decoding Specialized tRNA , 2002, Science.

[30]  R. Furter.  Expansion of the genetic code: Site‐directed p‐fluoro‐phenylalanine incorporation in Escherichia coli , 1998, Protein science : a publication of the Protein Society.

[31]  P. Schultz,et al.  Selective Staudinger Modification of Proteins Containing p‐Azidophenylalanine , 2005, Chembiochem : a European journal of chemical biology.

[32]  P. Schultz,et al.  Site-specific PEGylation of proteins containing unnatural amino acids. , 2004, Bioorganic & medicinal chemistry letters.

[33]  Peter G Schultz,et al.  Unnatural amino acid mutagenesis of green fluorescent protein. , 2003, The Journal of organic chemistry.

[34]  P. Schultz,et al.  Structural plasticity of an aminoacyl-tRNA synthetase active site. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[35]  P. Schultz,et al.  The incorporation of a photoisomerizable amino acid into proteins in E. coli. , 2006, Journal of the American Chemical Society.

[36]  Paul Schimmel,et al.  Incorporation of nonnatural amino acids into proteins. , 2004, Annual review of biochemistry.

[37]  P. Schultz,et al.  Site‐Specific in vivo Labeling of Proteins for NMR Studies , 2005, Chembiochem : a European journal of chemical biology.

[38]  S. Yokoyama,et al.  Protein photo-cross-linking in mammalian cells by site-specific incorporation of a photoreactive amino acid , 2005, Nature Methods.

[39]  Peter G Schultz,et al.  A phage display system with unnatural amino acids. , 2004, Journal of the American Chemical Society.

[40]  S. Boxer,et al.  Vibrational Stark effects calibrate the sensitivity of vibrational probes for electric fields in proteins. , 2003, Biochemistry.

[41]  P. Marlière,et al.  Enlarging the Amino Acid Set of Escherichia coli by Infiltration of the Valine Coding Pathway , 2001, Science.

[42]  H. Lester,et al.  Unnatural amino acid mutagenesis in mapping ion channel function , 2003, Current Opinion in Neurobiology.

[43]  P. Schultz,et al.  Expanding the genetic code. , 2002, Chemical communications.

[44]  R. Giegé,et al.  Major tyrosine identity determinants in Methanococcus jannaschii and Saccharomyces cerevisiae tRNA(Tyr) are conserved but expressed differently. , 2001, European journal of biochemistry.

[45]  S. Benzer,et al.  A change from nonsense to sense in the genetic code. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[46]  P. Schultz,et al.  Adaptation of an orthogonal archaeal leucyl-tRNA and synthetase pair for four-base, amber, and opal suppression. , 2003, Biochemistry.

[47]  P. Schultz,et al.  The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determination , 2004, Nature Biotechnology.

[48]  Peter G. Schultz,et al.  A New Strategy for the Synthesis of Glycoproteins , 2004, Science.

[49]  S. Yokoyama,et al.  Site-specific incorporation of an unnatural amino acid into proteins in mammalian cells. , 2002, Nucleic acids research.

[50]  David R. Liu,et al.  A New Functional Suppressor tRNA/ Aminoacyl-tRNA Synthetase Pair for the in Vivo Incorporation of Unnatural Amino Acids into Proteins , 2000 .

[51]  Peter G Schultz,et al.  Efficient incorporation of unnatural amino acids into proteins in Escherichia coli , 2006, Nature Methods.

[52]  P. Schultz,et al.  Substrate recognition by the AAA+ chaperone ClpB , 2004, Nature Structural &Molecular Biology.

[53]  P. Schultz,et al.  Adding L-3-(2-Naphthyl)alanine to the genetic code of E. coli. , 2002, Journal of the American Chemical Society.

[54]  P. Schultz,et al.  Addition of the keto functional group to the genetic code of Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[55]  P. Schimmel,et al.  Major Anticodon-binding Region Missing from an Archaebacterial tRNA Synthetase* , 1999, The Journal of Biological Chemistry.

[56]  U. RajBhandary,et al.  Twenty-first aminoacyl-tRNA synthetase–suppressor tRNA pairs for possible use in site-specific incorporation of amino acid analogues into proteins in eukaryotes and in eubacteria , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[57]  P. Schultz,et al.  A general approach for the generation of orthogonal tRNAs. , 2001, Chemistry & biology.

[58]  Shigeyuki Yokoyama,et al.  Structural basis for orthogonal tRNA specificities of tyrosyl-tRNA synthetases for genetic code expansion , 2003, Nature Structural Biology.

[59]  P. Schultz,et al.  Site-specific incorporation of a redox-active amino acid into proteins. , 2003, Journal of the American Chemical Society.

[60]  P. Schultz,et al.  Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Daisuke Kiga,et al.  An engineered Escherichia coli tyrosyl–tRNA synthetase for site-specific incorporation of an unnatural amino acid into proteins in eukaryotic translation and its application in a wheat germ cell-free system , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[62]  P. Schultz,et al.  The genetic incorporation of a distance probe into proteins in Escherichia coli. , 2006, Journal of the American Chemical Society.

[63]  R. Dwek,et al.  Glycosylation: heterogeneity and the 3D structure of proteins. , 1997, Critical reviews in biochemistry and molecular biology.

[64]  Peter G Schultz,et al.  Exploring the limits of codon and anticodon size. , 2002, Chemistry & biology.

[65]  Lei Wang,et al.  Crystal structures of apo wild‐type M. jannaschii tyrosyl‐tRNA synthetase (TyrRS) and an engineered TyrRS specific for O‐methyl‐L‐tyrosine , 2005, Protein science : a publication of the Protein Society.