Extending the Genetic Code

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Science  14 Jan 2000:
Vol. 287, Issue 5451, pp. 193
DOI: 10.1126/science.287.5451.193f

The genetic code maps the set of 64 three-base codons onto the canonical set of 20 amino acids. The incorporation of unnatural amino acids into proteins has been used to study structure and function, and to modify proteins in ways not accessible via enzymatic post-translational modification. In earlier work, a stop codon was re-programmed to add a single unnatural amino acid by using an amber suppressor transfer RNA (tRNA). More recently, a four-base codon and a frameshift suppressor tRNA (a chemically acylated version of yeast tRNAPhe) were utilized in similar fashion. Hohsaka et al. now report that different unnatural amino acids can be incorporated into the same protein, streptavidin, at two positions with the four-base codons AGGT and CGGG. Ribosomal synthesis of the full-length protein containing the two derivatized residues required both modified tRNAs; the omission of either resulted in a frameshift reversion to the three-base codon (either AGG or CGG) and premature termination at a nearby stop codon.—PDS

J. Am. Chem. Soc.121, 12194 (1999).

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