Protein organic chemistry and applications for labeling and engineering in live-cell systems

Yousuke Takaoka, Akio Ojida, Itaru Hamachi

Research output: Contribution to journalReview articlepeer-review

206 Citations (Scopus)

Abstract

The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both invitro and in live cells or invivo. Herein we review recent progress in chemistry-based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: 1)the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test-tube settings; 2)the bioorthogonal reactions of proteins with non-natural functional groups; 3)the coupling of recognition and reactive sites using an enzyme or short peptide tag-probe pair for labeling natural amino acids; and 4)ligand-directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chemical biology, with the methods 2-4 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of organic chemistry for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists. Labels of the reconstruction: Chemical modification of proteins with synthetic probes is a powerful means of elucidating protein functions in live cells and of influencing these functions. New reactions that can be successfully applied in living systems represent a worthy challenge to organic chemistry, especially as the labeling and manipulation of endogenous proteins in their natural habitats is currently at an early stage.

Original languageEnglish
Pages (from-to)4088-4106
Number of pages19
JournalAngewandte Chemie - International Edition
Volume52
Issue number15
DOIs
Publication statusPublished - 2013 Apr 8
Externally publishedYes

Keywords

  • bioconjugation
  • bioorthogonal chemistry
  • ligand-directed chemistry
  • protein engineering
  • protein labeling

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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