[Perspective] A radical approach to posttranslational mutagenesis
The structure and function of proteins is extensively modulated and expanded by posttranslational modifications (PTMs) on many of the canonical amino acids. As a means of unraveling the role and interplay of PTMs, methods to produce proteins with site-specific modifications have attracted considerable attention. In addition to PTMs, incorporation of unnatural side chains is of interest for protein engineering, and systematic studies using analogs of amino acids offer insights into the molecular mechanisms by which proteins and enzymes work. On pages 597 and 623 of this issue, Wright et al. (1) and Yang et al. (2) report potentially general strategies to chemically introduce a wide variety of natural, unnatural, posttranslationally modified, and labeled side chains via an unprecedented carbon-carbon bond-forming reaction on intact proteins. This approach will be of particular interest to chemical biologists aiming to introduce authentic protein PTMs, as well as to protein chemists interested in introducing unnatural...