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Methods and compositions for the production of orthogonal tRNA-aminoacyl-tRNA synthetase pairs

Patent ·
OSTI ID:1027459
 [1];  [2];  [2];  [2];  [3];  [4];  [5];  [2];  [2];  [2];  [2]
  1. La Jolla, CA
  2. San Diego, CA
  3. Lexington, MA
  4. North Haven, CT
  5. Philadelphia, PA
+ Show Author Affiliations

This invention provides compositions and methods for generating components of protein biosynthetic machinery including orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases. Methods for identifying orthogonal pairs are also provided. These components can be used to incorporate unnatural amino acids into proteins in vivo.

Research Organization:
The Scripps Research Institute (La Jolla, CA)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG03-00ER45812; AC03-76SF00098
Assignee:
The Scripps Research Institute (La Jolla, CA); The Regents of the University of California (Oakland, CA)
Patent Number(s):
8,012,739
Application Number:
11/978,154
OSTI ID:
1027459
Country of Publication:
United States
Language:
English

References (109)

Backbone Mutations in Transmembrane Domains of a Ligand-Gated Ion Channel journal January 1999
Glutamine analogues as potential antimalarials journal March 1991
Crystal structure of the dipeptide binding protein from Escherichia coli involved in active transport and chemotaxis journal November 1995
Synthesis of novel α-amino-acids and derivatives using radical chemistry: synthesis of L- and D-α-amino-adipic acids, L-α journal January 1987
Illicit Transport: The Oligopeptide Permease journal February 1973
Expansion of the genetic code: Site-directed p-fluoro-phenylalanine incorporation in Escherichia coli journal February 1998
An efficient system for the evolution of aminoacyl-tRNA synthetase specificity journal September 2002
Differences in Backbone Structure between Angiotensin II Agonists and Type I Antagonists journal November 1995
Evolutionary relationship between Halobacterium cutirubrum and eukaryotes determined by use of aminoacyl-tRNA synthetases as phylogenetic probes journal March 1980
Aminoacyl-tRNA synthetases: Versatile players in the changing theater of translation journal November 2002
Protein Engineering by In Vivo Incorporation of Non-Natural Amino Acids: Control of Incorporation of Methionine Analogues by Methionyl-tRNA Synthetase journal November 2000
Adding l-3-(2-Naphthyl)alanine to the Genetic Code of E. coli journal March 2002
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 journal July 2002
Quantitation of Transcription and Clonal Selection of Single Living Cells with -Lactamase as Reporter journal January 1998
Biosynthetic site-specific incorporation of a non-natural amino acid into a polypeptide journal September 1989
Site-Specific Protein Modification Using a Ketone Handle
  • Cornish, Virginia W.; Hahn, Klaus M.; Schultz, Peter G.
  • Journal of the American Chemical Society, Vol. 118, Issue 34, p. 8150-8151 https://doi.org/10.1021/ja961216x
journal January 1996
A synthetic IgG-binding domain based on staphylococcal protein A journal January 1987
Strategies for in vitro and in vivo translation with non-natural amino acids journal December 1996
Compilation of tRNA sequences and sequences of tRNA genes journal January 1998
Construction of Escherichia coli amber suppressor tRNA genes: II. Synthesis of additional tRNA genes and improvement of suppressor efficiency journal June 1990
Expanding the genetic code: selection of efficient suppressors of four-base codons and identification of “shifty” four-base codons with a library approach in Escherichia coli journal March 2001
Probing the Structure and Function of the Tachykinin Neurokinin-2 Receptor through Biosynthetic Incorporation of Fluorescent Amino Acids at Specific Sites journal August 1996
Exploiting unassigned codons in Micrococcus luteus for tRNA-based amino acid mutagenesis journal November 1997
Aspartate identity of transfer RNAs journal January 1996
Efforts toward Expansion of the Genetic Alphabet:  DNA Polymerase Recognition of a Highly Stable, Self-Pairing Hydrophobic Base journal December 1999
Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells journal April 1995
A set of plasmids constitutively producing different RNA levels in Escherichia coli journal July 1999
Editing of errors in selection of amino acids for protein synthesis. journal January 1992
Toward the experimental codon reassignment in vivo : protein building with an expanded amino acid repertoire journal January 1999
Novel Biological Process for L-DOPA Production from L-Tyrosine by P-Hydroxyphenylacetate 3-Hydroxylase journal January 1998
Bio–incorporation of telluromethionine into buried residues of dihydrofolate reductase journal May 1994
2 .ANG. Resolution Structure of DppA, a Periplasmic Dipeptide Transport/Chemosensory Receptor journal December 1995
Region of a Conserved Sequence Motif in a Class II tRNA Synthetase Needed for Transfer of an Activated Amino Acid to an RNA Substrate journal May 1994
Substrate Specificity Is Determined by Amino Acid Binding Pocket Size in Escherichia coli Phenylalanyl-tRNA Synthetase journal June 1994
Rational Design of an Unnatural Base Pair with Increased Kinetic Selectivity journal September 2000
Incorporation of Trifluoromethionine into a Phage Lysozyme:  Implications and a New Marker for Use in Protein 19 F NMR † journal March 1997
Protein-protein interaction: a genetic selection for compensating mutations at the barnase-barstar interface. journal March 1996
Synthesis of Derivatives of Glutamine as Model Substrates for Anti-tumor Agents journal July 1959
Changing the Amino Acid Specificity of Yeast Tyrosyl-tRNA Synthetase by Genetic Engineering journal September 2001
A Novel Copper-Mediated DNA Base Pair
  • Meggers, Eric; Holland, Patrick L.; Tolman, William B.
  • Journal of the American Chemical Society, Vol. 122, Issue 43, p. 10714-10715 https://doi.org/10.1021/ja0025806
journal November 2000
Transfer RNA-dependent cognate amino acid recognition by an aminoacyl-tRNA synthetase. journal April 1996
Major tyrosine identity determinants in Methanococcus jannaschii and Saccharomyces cerevisiae tRNA Tyr are conserved but expressed differently : tRNA identity for journal February 2001
A general method for site-specific incorporation of unnatural amino acids into proteins journal April 1989
Libraries of hybrid proteins from distantly related sequences journal May 2001
A New Functional Suppressor tRNA/Aminoacyl−tRNA Synthetase Pair for the in Vivo Incorporation of Unnatural Amino Acids into Proteins journal May 2000
An unnatural base pair for incorporating amino acid analogs into proteins journal February 2002
Enzymatic incorporation of a new base pair into DNA and RNA extends the genetic alphabet journal January 1990
Phage selection for site-specific incorporation of unnatural amino acids into proteins in vivo journal September 2001
Progress toward the evolution of an organism with an expanded genetic code journal April 1999
Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD): a vehicle for direct determination of three-dimensional structure. journal May 1990
Universal rules and idiosyncratic features in tRNA identity journal November 1998
5′–3′ Exonucleases in phosphorothioate-based oligonucleotide-directed mutagenesis journal January 1988
Expanding the Genetic Code of Escherichia coli journal April 2001
Enzymatic incorporation of a new base pair into DNA and RNA journal October 1989
Major Anticodon-binding Region Missing from an Archaebacterial tRNA Synthetase journal December 1999
A New Orthogonal Suppressor tRNA/Aminoacyl-tRNA Synthetase Pair for Evolving an Organism with an Expanded Genetic Code journal September 2000
Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to protein-reactive drugs and metabolites: criteria for identification of antibody activity journal April 1986
Efforts toward Expansion of the Genetic Alphabet:  Replication of DNA with Three Base Pairs journal August 2001
Genetic analysis of amino acid transport in the facultatively heterotrophic cyanobacterium Synechocystis sp. strain 6803. journal October 1987
Synthesis of optically pure pipecolates from L-asparagine. Application to the total synthesis of (+)-apovincamine through amino acid decarbonylation and iminium ion cyclization journal April 1985
Absolute configuration of the enantiomers of 7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline (chloroquine) journal March 1988
The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene journal October 2001
Incorporation of Nonnatural Amino Acids Into Proteins journal June 2004
In vitro protein engineering using synthetic tRNAAla with different anticodons journal August 1993
Engineering a tRNA and aminoacyl-tRNA synthetase for the site-specific incorporation of unnatural amino acids into proteins in vivo journal September 1997
Human Tyrosyl-tRNA Synthetase Shares Amino Acid Sequence Homology with a Putative Cytokine journal May 1997
Genetic code in evolution: switching species-specific aminoacylation with a peptide transplant journal January 1998
Synthesis of 4-substituted prolines as conformationally constrained amino acid analogs journal April 1989
An Engineered Tetrahymena tRNA Gln for in Vivo Incorporation of Unnatural Amino Acids into Proteins by Nonsense Suppression journal September 1996
TRNA2Gln Su+2 mutants that increase amber suppression. journal January 1981
Relaxing the substrate specificity of an aminoacyl-tRNA synthetase allows in vitro and in vivo synthesis of proteins containing unnatural amino acids journal May 1995
Quisqualic acid analogs: synthesis of .beta.-heterocyclic 2-aminopropanoic acid derivatives and their activity at a novel quisqualate-sensitized site journal November 1992
Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme journal July 1998
Site-specific incorporation of novel backbone structures into proteins journal January 1992
Unprotected Peptides as Building Blocks for the Synthesis of Peptide Dendrimers with Oxime, Hydrazone, and Thiazolidine Linkages journal April 1995
Efficient introduction of alkene functionality into proteins in vivo journal May 1998
Photocrosslinking of the signal sequence of nascent preprolactin to the 54-kilodalton polypeptide of the signal recognition particle. journal November 1986
High-level Biosynthetic Substitution of Methionine in Proteins by its Analogs 2-Aminohexanoic Acid, Selenomethionine, Telluromethionine and Ethionine in Escherichia coli journal June 1995
New Photolabeling and Crosslinking Methods journal June 1993
Mutational Analysis of Invariant Valine B12 in Insulin:  Implications for Receptor Binding journal November 2000
Expanding the genetic code journal December 2001
A new code for life: Expansion of the genetic code and artificial assembly of functional genomes are raising important questions about ethics and safety journal April 2004
Production and fluorescence-activated cell sorting of Escherichia coli expressing a functional antibody fragment on the external surface. journal November 1993
C EREAL C HROMOSOME S TRUCTURE , E VOLUTION, AND P AIRING journal June 2000
Highly Precise Shape Mimicry by a Difluorotoluene Deoxynucleoside, a Replication-Competent Substitute for Thymidine journal January 1997
Rescuing an essential enzyme-RNA complex with a non-essential appended domain journal May 1997
[15] Biosynthetic method for introducing unnatural amino acids site-specifically into proteins book January 1991
Site-Directed Mutagenesis with an Expanded Genetic Code journal June 1995
Efficient introduction of aryl bromide functionality into proteins in vivo journal February 2000
Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting. journal October 1989
Enzyme-generated intracellular fluorescence for single-cell reporter gene analysis utilizing Escherichia coli β-glucuronidase journal August 1996
693. A new synthesis of glutamine and of γ-dipeptides of glutamic acid from phthalylated intermediates journal January 1949
Modification of the amino acid specificity of tyrosyl-tRNA synthetase by protein engineering journal March 1993
Exploring the Limits of Codon and Anticodon Size journal February 2002
Enlarging the Amino Acid Set of Escherichia coli by Infiltration of the Valine Coding Pathway journal April 2001
Translational efficiency of transfer RNA's: uses of an extended anticodon journal November 1982
A binding protein for l-glutamine and its relation to active transport in E. coli journal February 1971
Flash Decaging of Tyrosine Sidechains in an Ion Channel journal April 1998
A Mutant Escherichia coli Tyrosyl-tRNA Synthetase Utilizes the Unnatural Amino Acid Azatyrosine More Efficiently than Tyrosine journal September 2000
Transport and Hydrolysis of Antibacterial Peptide Analogues in Escherichia coli: Backbone-modified Aminoxy Peptides journal September 1984
Co-Expression of Yeast Amber Suppressor tRNATyr and Tyrosyl-tRNA Synthetase in Escherichia coli: Possibility to Expand the Genetic Code journal December 1998
Efficient Incorporation of Nonnatural Amino Acids with Large Aromatic Groups into Streptavidin in In Vitro Protein Synthesizing Systems journal January 1999
Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs journal September 1990
Noninvasive Tracing of Recombinant Proteins with “Fluorophenylalanine-Fingers” journal August 2000
Probing Protein Structure and Function with an Expanded Genetic Code journal March 1995
A general approach for the generation of orthogonal tRNAs journal September 2001
Efficient Incorporation of Unsaturated Methionine Analogues into Proteins in Vivo journal February 2000
Efforts toward the Expansion of the Genetic Alphabet:  Information Storage and Replication with Unnatural Hydrophobic Base Pairs journal April 2000
Crystal structure of yeast phenylalanine transfer RNA: I. Crystallographic refinement journal August 1978

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