Selenium chemistry for spatio-selective peptide and protein functionalization

The ability to construct a peptide or protein in a spatio-specific manner is of great interest for therapeutic and biochemical research. However, the various functional groups present in peptide sequences and the need to perform chemistry under mild and aqueous conditions make selective protein functionalization one of the greatest synthetic challenges. The fascinating paradox of selenium (Se) — being found in both toxic compounds and also harnessed by nature for essential biochemical processes — has inspired the recent exploration of selenium chemistry for site-selective functionalization of peptides and proteins. In this Review, we discuss such approaches, including metal-free and metal-catalysed transformations, as well as traceless chemical modifications. We report their advantages, limitations and applications, as well as future research avenues.