Highly Efficient and Site-Selective Phosphane Modification of Proteins through Hydrazone Linkage: Development of Artificial Metalloenzymes

A joint effort: A novel, highly efficient, and selective procedure for phosphane modification of proteins is reported (see scheme). This method involves cysteine modification with a maleimide containing a hydrazide functional group and subsequent hydrazone formation with phosphane aldehydes. Mono‐ and bidentate phosphane ligands were successfully coupled to several proteins, one of which was coordinated to rhodium to give an artificial metalloenzyme.