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US 7,638,300 B2Granted
In vivo incorporation of unnatural amino acids
AssigneesThe Scripps Research Institute, The Regents of the University of California
InventorsPeter Schultz, Lei Wang, John Christopher Anderson, Jason W. Chin, David R. Liu, Thomas J. Magliery, Eric Meggers, Ryan Aaron Mehl, Miro Pastrnak
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Abstract
The invention provides methods and compositions for in vivo incorporation of unnatural amino acids. Also provided are compositions including proteins with unnatural amino acids.
Claims2
An isolated host cell, comprising:
- an unnatural amino acid having the structure of Formula I, wherein R is any substituent other than a substituent of any natural amino acid and wherein the unnatural amino acid is a tyrosine analogue or a phenylalanine analogue;
- a tyrosyl orthogonal tRNA (O-tRNA);
- an orthogonal aminoacyl tRNA synthetase (O—RS), wherein the ORS is derived from a tyrosyl ORS and wherein the O—RS preferentially aminoacylates the O-tRNA with the unnatural amino acid;
- wherein the Km of the ORS for the unnatural amino acid is lower than for any naturally occurring amino acid;
- wherein the kcat of the ORS for aminoacylation of the O-tRNA with the unnatural amino acid is higher than aminoacylation of the O-tRNA with any naturally occurring amino acid;
- wherein an mRNA that comprises a selector codon is specifically recognized by the O-tRNA;
- and wherein the mRNA encodes a human serum albumin (HSA) polypeptide, which mRNA comprises at least one selector codon that is recognized by the O-tRNA.
4 more elements
Dependencies are inferred from the claim text.