Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (13): 1439-1445.DOI: 10.6023/A12050263 Previous Articles     Next Articles



李劼, 王杰, 陈鹏   

  1. 北京大学化学生物学系 北京 100871
  • 投稿日期:2012-05-31 发布日期:2012-06-19
  • 通讯作者: 陈鹏
  • 基金资助:

    项目受科技部重大科学研究计划(Nos. 2010CB912300 and 2012CB917300)和国家自然科学基金委重大研究计划培育项目(Nos. 91013005 and 21001010)资助.

Unnatural Amino Acid Mediated Protein Bioorthogonal Labeling

Li Jie, Wang Jie, Chen Peng R.   

  1. Department of Chemical Biology, Peking University, Beijing 100871
  • Received:2012-05-31 Published:2012-06-19
  • Supported by:

    Project supported by the National Key Basic Research Foundation of China (Nos. 2010CB912300 and 2012CB917300) and the National Natural Science Foundation of China (Nos. 91013005 and 21001010).

The bioorthogonal chemistry has become a valuable tool for specific labeling of biomolecules in living systems. One emerging example is to convert the palladium-mediated carbon-carbon bond formation reaction, a landmark reaction in organic synthesis, into the biocompatible reaction for biomolecule modifications. A prerequisite to enable such reactions to be executed on biological samples is to incorporate the corresponding bioorthogonal functional groups into target biomolecules. The genetic code expansion strategy is a leading technology on introducing diverse bioorthogonal functionalities into proteins, and the most recently developed pyrrolysine system can now allow unnatural amino acids (UAAs) bearing bioorthogonal handles into proteins in prokaryotic cells, eukaryotic cells and even in living animals. In this perspective, we will first introduce some of the forefronts of the bioorthognal reactions as well as the genetic code expansion strategy. We then will discuss the advantages and attractiveness of combining these newly emerged tools, Pd-mediated biomolecular labeling and pyrrolysine-based genetic code expansion system in particular, to specifically label and study proteins in living mammalian cells. More biocompatible reactions and more flexible UAA incorporation system will significantly strengthen and expand our ability to specifically manipulate proteins in their native cellular environment.

Key words: protein labeling, bioothorgonal, palladium catalyzed, cross coupling, unnatural amino acid