Abstract
Chemical protein modification is a powerful technique not only for elucidating protein functions but also for providing new tools to explore complicated biological processes in live cells. The progress of modern organic chemistry and bio-orthogonal chemistry has enabled the synthesis of artificial probe-protein conjugates with a site-specific and target-selective manner in crude environments. With the advent of ligand-directed chemistry, it is now possible to directly modify “endogenous” proteins of interest in live cells and even in animals. Furthermore, combining chemistry-based protein labeling with the latest analytical methods facilitates to comprehensive studies of proteomes of complex biological samples. In this review, we focus the recent studies in synthetic organic chemistry for protein labeling. We survey the methods for both target-selective labeling and global labeling of proteins, and describe these applications toward in situ engineering and analysis of proteins in their native habitats. Current limitations and future directions of this research area are also discussed.
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