Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

The invention provides methods and compositions for a mutein aminoacyl-tRNA synthetase that preferentially charges a tRNA with a non-natural amino acid. Also provided are methods for incorporating the non-natural amino acids, pyridinyl-amino tetrazine amino acids, into a protein, and further conjugating a biologically active adduct to the pyridinyl-amino tetrazine.

The invention provides methods and compositions for a mutein aminoacyl-tRNA synthetase that preferentially charges a tRNA with a non-natural amino acid. Also provided are methods for incorporating the non-natural amino acid, para-methylazido-L-phenylalanine into a protein and further conjugating a biologically active adduct to the para-methylazido-L-phenylalanine.

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Tetrazine non-canonical amino acids, methods for genetic encoding proteins and polypeptides using the tetrazine amino acids, proteins and polypeptides comprising the tetrazine amino acids, and compositions comprising the proteins and polypeptides having at least one post-translational modification thereof comprising in vivo reaction with the incorporated tetrazine amino acid and a second molecule.

Provided in the present invention are a method for constructing a strain for producing a recombinant protein containing unnatural amino acids, and the strain obtained therefrom. The method comprises modifying the expression of a prfA gene contained in the strain to be controllable. The strain constructed by the method of the present invention can efficiently produce in intact protein containing unnatural amino acids, greatly reduce the production of a truncated protein and can also maintain high-speed growth.

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

There are provided amino acid derivatives of formula V and VI as defined herein which are pyrrolysine analogs for use in bioconjugation processes.

There is provided inter alia a process for stabilizing a eukaryotic cell line which expresses PylRS and tRNAPyl and which is suitable for incorporation of a gene encoding a target protein containing one or more non-natural amino acids encoded by a nonsense codon which comprises culturing said cell line under conditions in which the adverse effect of tRNAPyl expression on cell viability and/or cell growth is reduced or eliminated.

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.