A cysteine selenosulfide redox switch for protein chemical synthesis
Vincent Diemer, Nathalie Ollivier, Bérénice Leclercq, Hervé Drobecq, Jérôme Vicogne, Vangelis Agouridas, Oleg Melnyk
Received Date: 14th November 19
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 backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor mimics.
Read in full at ChemRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.