Olefin Metathesis for Site‐Selective Protein Modification

Protein compatible . Olefin metathesis has emerged as a viable strategy for site‐selective protein modification. This minireview traces its development from early peptide models and metathesis in water to its ultimate application to protein substrates. Prospects in chemistry and biology are also discussed. magnified image For a reaction to be generally useful for protein modification, it must be site‐selective and efficient under conditions compatible with proteins: aqueous media, low to ambient temperature, and at or near neutral pH. To engineer a reaction that satisfies these conditions is not a simple task. Olefin metathesis is one of most useful reactions for carbon–carbon bond formation, but does it fit these requirements? This minireview is an account of the development of olefin metathesis for protein modification. Highlighted below are examples of olefin metathesis in peptidic systems and in aqueous media that laid the groundwork for successful metathesis on protein substrates. Also discussed are the opportunities in protein engineering for the genetic introduction of amino acids suitable for metathesis and the related challenges in chemistry and biology.