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  • 标题:Protein evolution with an expanded genetic code
  • 本地全文:下载
  • 作者:Chang C. Liu ; Antha V. Mack ; Meng-Lin Tsao
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2008
  • 卷号:105
  • 期号:46
  • 页码:17688-17693
  • DOI:10.1073/pnas.0809543105
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:We have devised a phage display system in which an expanded genetic code is available for directed evolution. This system allows selection to yield proteins containing unnatural amino acids should such sequences functionally outperform ones containing only the 20 canonical amino acids. We have optimized this system for use with several unnatural amino acids and provide a demonstration of its utility through the selection of anti-gp120 antibodies. One such phage-displayed antibody, selected from a naive germline scFv antibody library in which six residues in VH CDR3 were randomized, contains sulfotyrosine and binds gp120 more effectively than a similarly displayed known sulfated antibody isolated from human serum. These experiments suggest that an expanded "synthetic" genetic code can confer a selective advantage in the directed evolution of proteins with specific properties.
  • 关键词:directed evolution ; phage display ; unnatural amino acids
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