Cited by 1,019RNA and protein synthesis mechanismsChemical Synthesis and AnalysisEnzyme Catalysis and Immobilization

A General Method for Site-specific Incorporation of Unnatural Amino Acids into Proteins

Noren, Christopher J., Anthony-Cahill, Spencer J., Griffith, Michael C., Schultz, Peter G.·1989·Science

Abstract

A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins. Synthetic amino acids were incorporated into the enzyme β-lactamase by the use of a chemically acylated suppressor transfer RNA that inserted the amino acid in response to a stop codon substituted for the codon encoding residue of interest. Peptide mapping localized the inserted amino acid to a single peptide, and enough enzyme could be generated for purification to homogeneity. The catalytic properties of several mutants at the conserved Phe 66 were characterized. The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function.

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Crossref · 10.1126/science.2649980

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  • Experiments have demonstrated that the machinery of known life can be manipulated to incorporate many nonbiological amino acids into proteins during translation.

    “Experiments have demonstrated that the machinery of known life can be manipulated to incorporate many nonbiological amino acids into proteins during translation (Bain et al., 1989; Noren et al., 1989; Chin et al., 2003).”

    From The Astrobiology Primer v2.0 (2016) · cites this paper as Noren et al., 1989

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References 72 · Cited by 1,019

Authors
Noren, C. J., Anthony-Cahill, S. J., Griffith, M. C., & Schultz, P. G.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • Department of Chemistry, University of California, Berkeley, CA 94720, and the Center for Advanced Materials, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Venue
Science
Published
1989-04-14
Volume
244
Issue
4901
Pages
182-188
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2067013502
Cited by
1,019
References
72
Citations by year
2026: 18 · 2025: 16 · 2024: 34 · 2023: 25 · 2022: 28 · 2021: 44 · 2020: 34 · 2019: 37 · 2018: 26 · 2017: 19 · 2016: 25 · 2015: 37 · 2014: 38 · 2013: 39 · 2012: 30
FWCI
6.45
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
Keywords
beta-lactamase, suppressor tRNA, catalytic properties, protein engineering, synthetic amino acids
MeSH terms
Amino Acids, beta-Lactamases, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Mutation, Proteins, RNA, Transfer, Protein Biosynthesis

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