Expanding the genetic lexicon: incorporating non-standard amino acids into proteins by ribosome-based synthesis.

Only 20 amino acids are normally incorporated into proteins synthesized in living cells, and this has limited the structural range of proteins that can be prepared. New methods that allow the incorporation of amino acids that are not normally encoded by natural genes are being developed: these include reassigning functions within the existing genetic code, and expanding the genetic code by constructing additional, non-natural codons. Used in conjunction with recent major advances in understanding protein structure-function relationships, these approaches should extend the range of de novo protein designs that are possible.

[1]  S. Osawa,et al.  Recent evidence for evolution of the genetic code , 1992, Microbiological reviews.

[2]  J. Hoch,et al.  Characterization of the structural properties of .alpha.1B, a peptide designed to form a four-helix bundle , 1992 .

[3]  P. Kast,et al.  Amino acid substrate specificity of Escherichia coli phenylalanyl-tRNA synthetase altered by distinct mutations. , 1991, Journal of molecular biology.

[4]  D. L. Veenstra,et al.  Probing protein stability with unnatural amino acids. , 1992, Science.

[5]  Janet M. Thornton,et al.  Prediction of progress at last , 1991, Nature.

[6]  D. Wemmer,et al.  Site-specific isotopic labeling of proteins for NMR studies , 1992 .

[7]  J. Knowles Tinkering with enzymes: what are we learning? , 1987, Science.

[8]  B. Golding,et al.  Molecular mechanisms in bioorganic processes , 1990 .

[9]  S. Benner,et al.  Patterns of divergence in homologous proteins as indicators of secondary and tertiary structure: a prediction of the structure of the catalytic domain of protein kinases. , 1991, Advances in enzyme regulation.

[10]  R. Hodges,et al.  Relationship between amide proton chemical shifts and hydrogen bonding in amphipathic .alpha.-helical peptides , 1992 .

[11]  S. Benner,et al.  A C-nucleotide base pair: methylpseudouridine-directed incorporation of formycin triphosphate into RNA catalyzed by T7 RNA polymerase. , 1991, Biochemistry.

[12]  P. Schultz,et al.  Protein biosynthesis with conformationally restricted amino acids , 1993 .

[13]  Richard Chamberlin,et al.  Ribosome-mediated incorporation of a non-standard amino acid into a peptide through expansion of the genetic code , 1992, Nature.

[14]  S A Benner,et al.  Predicted secondary structure for the Src homology 3 domain. , 1993, Journal of molecular biology.

[15]  B. Gutte,et al.  Design, synthesis and characterisation of a 34-residue polypeptide that interacts with nucleic acids , 1979, Nature.

[16]  P. Schultz,et al.  Probing the structure and mechanism of Ras protein with an expanded genetic code. , 1993, Science.

[17]  P. Harrison,et al.  The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA. , 1986, The EMBO journal.

[18]  J. Richardson,et al.  De novo design, expression, and characterization of Felix: a four-helix bundle protein of native-like sequence. , 1990, Science.

[19]  G. Barton,et al.  Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains , 1992, FEBS letters.

[20]  W. Tate,et al.  Characterization of reticulocyte release factor. , 1977, The Journal of biological chemistry.

[21]  S. Benner,et al.  Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides , 1993, Nature.

[22]  A. Chamberlin,et al.  Site-specific incorporation of non-natural residues into peptides: Effect of residue structure on suppression and translation efficiencies , 1991 .

[23]  S. Hecht,et al.  Ribosome-catalyzed formation of an abnormal peptide analogue. , 1986, Biochemistry.

[24]  P G Schultz,et al.  A general method for site-specific incorporation of unnatural amino acids into proteins. , 1989, Science.

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

[26]  S. Benner,et al.  A secondary structure prediction of the hemorrhagic metalloprotease family. , 1993, Biochemical and biophysical research communications.

[27]  D Eisenberg,et al.  Crystal structure of a synthetic triple-stranded alpha-helical bundle. , 1993, Science.

[28]  Steven A. Benner,et al.  Enzymatic incorporation of a new base pair into DNA and RNA , 1989 .

[29]  S. Benner,et al.  Total synthesis and cloning of a gene coding for the ribonuclease S protein. , 1984, Science.

[30]  S A Benner,et al.  The nitrogenase MoFe protein , 1993, FEBS letters.

[31]  S. Kent,et al.  Total chemical synthesis of a D-enzyme: the enantiomers of HIV-1 protease show reciprocal chiral substrate specificity [corrected]. , 1992, Science.

[32]  J. Zheng,et al.  Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. , 1991, Science.

[33]  S. Hecht,et al.  "Chemical aminoacylation" of tRNA's. , 1978, The Journal of biological chemistry.

[34]  J H Miller,et al.  Genetic studies of the lac repressor. IX. Generation of altered proteins by the suppression of nonsence mutations. , 1979, Journal of molecular biology.

[35]  P. Schultz,et al.  A general and efficient route for chemical aminoacylation of transfer RNAs , 1991 .

[36]  Steven A. Benner,et al.  Enzymatic incorporation of a new base pair into DNA and RNA extends the genetic alphabet , 1990, Nature.

[37]  B. Martoglio,et al.  Mischarging Escherichia coli tRNAPhe with L-4'-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenylalanine, a photoactivatable analogue of phenylalanine. , 1988, Biochemistry.