Evolution of proteins with genetically encoded "chemical warheads"

Chang C. Liu, Antha V. Mack, Eric M. Brustad, Jeremy Mills, Dan Groff, Vaughn V. Smider, Peter G. Schultz

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

(Chemical Equation Presented) We recently developed a phage-based system for the evolution of proteins in bacteria with expanded amino acid genetic codes. Here we demonstrate that the unnatural amino acid p-boronophenylalanine (BF) confers a selective advantage in the evolution of glycan-binding proteins. We show that an unbiased library of naïve antibodies with NNK-randomized VH CDR3 loops converges upon mutants containing BF when placed under selection for binding to a model acyclic amino sugar. This work represents a first step in the evolution of carbohydrate-binding proteins that use a reactive unnatural amino acid "warhead" and demonstrates that a "synthetic" genetic code can confer a selective advantage by increasing the number of functional groups available to evolution.

Original languageEnglish (US)
Pages (from-to)9616-9617
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number28
DOIs
StatePublished - Jul 22 2009
Externally publishedYes

Fingerprint

Genetic Code
Amino acids
Proteins
Amino Acids
Amino sugars
Amino Sugars
Bacteriophages
Carbohydrates
Antibodies
Functional groups
Polysaccharides
Bacteria
Carrier Proteins
saccharide-binding proteins
4-boronophenylalanine

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Liu, C. C., Mack, A. V., Brustad, E. M., Mills, J., Groff, D., Smider, V. V., & Schultz, P. G. (2009). Evolution of proteins with genetically encoded "chemical warheads". Journal of the American Chemical Society, 131(28), 9616-9617. https://doi.org/10.1021/ja902985e

Evolution of proteins with genetically encoded "chemical warheads". / Liu, Chang C.; Mack, Antha V.; Brustad, Eric M.; Mills, Jeremy; Groff, Dan; Smider, Vaughn V.; Schultz, Peter G.

In: Journal of the American Chemical Society, Vol. 131, No. 28, 22.07.2009, p. 9616-9617.

Research output: Contribution to journalArticle

Liu, CC, Mack, AV, Brustad, EM, Mills, J, Groff, D, Smider, VV & Schultz, PG 2009, 'Evolution of proteins with genetically encoded "chemical warheads"', Journal of the American Chemical Society, vol. 131, no. 28, pp. 9616-9617. https://doi.org/10.1021/ja902985e
Liu, Chang C. ; Mack, Antha V. ; Brustad, Eric M. ; Mills, Jeremy ; Groff, Dan ; Smider, Vaughn V. ; Schultz, Peter G. / Evolution of proteins with genetically encoded "chemical warheads". In: Journal of the American Chemical Society. 2009 ; Vol. 131, No. 28. pp. 9616-9617.
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