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Davis/Anthony paper describes system that enables enzyme-free site-selective cleavage of dehydroalanine tagged proteins

The ability of proteins to self-modify is rare, but the capability to design a chemically induced targeted proteolytic cleavage site would be enormously advantageous in many biotechnology applications and for the development of new medicines. In a proof-of-principle study, a team from the laboratories of Ben Davis and Daniel Anthony have designed and tested a system that enables enzyme-free site-selective cleavage of dehydroalanine tagged proteins. The reaction is promoted by diboron and is achievable under mild aqueous conditions. Usefully, it can be used to generate C-terminal amidation, which is essential for the activity of a number of important neuropeptides that are currently hard to synthesise. Indeed, drawing upon classical organ bath preparations  that are available in Pharmacology, the team showed that it was possible to generate pharmacologically active neurokinin-A from a proteome lysate containing precursors following the incorporation of the chemically sensitive cleavage site. Professor Davis speculates that “this ability to achieve site-directed chemical modification of proteins sets the scene to stimulate new and exciting modes of synthetic biology and unpick some intriguing mechasnisms.”

The full paper, ‘Reductive site-selective atypical C,Z-type / N2–C2 cleavage allows C-terminal protein amidation’, is available open-access in Science Advances, a leading multidisciplinary journal with a global readership, which can be read at