Electrochemistry for the Chemoselective Modification of Peptides and Proteins

Although electrochemical strategies for small-molecule synthesis are flourishing, this technology has yet to be fully exploited for the mild and chemoselective modification of peptides and proteins. With the growing number of diverse peptide natural products being identified and the emergence of modified proteins as therapeutic and diagnostic agents, methods for electrochemical modification stand as alluring prospects for harnessing the reactivity of polypeptides to build molecular complexity. As a mild and inherently tunable reaction platform, electrochemistry is arguably well-suited to overcome the chemo- and regioselectivity issues which limit existing bioconjugation strategies. This Perspective will showcase recently developed electrochemical approaches to peptide and protein modification. The article also highlights the wealth of untapped opportunities for the production of homogeneously modified biomolecules, with an eye toward realizing the enormous potential of electrochemistry for chemoselective bioconjugation chemistry.