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A Cysteine Selenosulfide Redox Switch for Protein Chemical Synthesis

revised on 26.02.2020, 11:31 and posted on 26.02.2020, 11:40 by Vincent Diemer, Nathalie Ollivier, Bérénice Leclercq, Hervé Drobecq, Jérôme Vicogne, Vangelis Agouridas, Oleg Melnyk
The control of cysteine reactivity is of paramount importance for the synthesis of proteins using the native chemical ligation (NCL) reaction. We discovered that this goal can be achieved in a traceless manner during ligation by appending a simple N-selenoethyl group to cysteine. While in synthetic organic chemistry the cleavage of carbon-nitrogen bonds is notoriously difficult, we found that N-selenoethyl cysteine (SetCys) loses its selenoethyl arm in water under mild conditions upon reduction of its selenosulfide bond. Detailed mechanistic investigations uncover a novel mode of reactivity for Cys. Its implementation in a process enabling the modular and straightforward assembly of linear or backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor variants.




Email Address of Submitting Author


CNRS, Université de Lille, INSERM, Institut Pasteur de Lille



ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing interests.