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Evolution of proteins with genetically encoded "chemical warheads".

ABSTRACT: 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 naive antibodies with NNK-randomized V(H) 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.

SUBMITTER: Liu CC

PROVIDER: S-EPMC2745334 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Evolution of proteins with genetically encoded "chemical warheads".

Liu Chang C CC Mack Antha V AV Brustad Eric M EM Mills Jeremy H JH Groff Dan D Smider Vaughn V VV Schultz Peter G PG

Journal of the American Chemical Society 20090701 28

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 naive antibodies with NNK-randomized V(H) CDR3 loops converges upon mutants containing BF when placed under selection for binding to a model acyclic amino sugar. This work represents a fi ...[more]

PMID: 19555063

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