Evolution of proteins with genetically encoded "chemical warheads"

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

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


(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
Issue number28
StatePublished - Jul 22 2009
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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