Expanding the Toolbox of Chemoselective Modifications of Protein-Like Polymers at Methionine Residues

Marie Rosselin (1, 2) , Ye Xiao (1, 2) , Ludovic Belhomme (1, 2) , Sébastien Lecommandoux (1, 2) , Elisabeth Garanger (1, 2)

1 LCPO - Laboratoire de Chimie des Polymères Organiques
2 Team 3 LCPO : Polymer Self-Assembly & Life Sciences

Selective modifications at methionyl residues in proteins have attracted particular attention in recent years. Previously described methods to chemoselectively modify the methionine side chain in elastin-like polypeptides (ELPs) involved nucleophilic addition using alkyl halides or epoxides yielding a sulfonium group with a positive charge strongly affecting ELPs’ physicochemical properties, in particular their thermal responsiveness. We herein explored the recently reported ReACT method (Redox-Activated Chemical Tagging) based on the use of oxaziridine derivatives, yielding an uncharged sulfimide as an alternative route for chemoselective modifications of methionine-containing ELPs in aqueous medium. The different synthetic strategies are herein compared in order to provide a furnished toolbox for further biorthogonal postmodifications of any protein polymers.

Keywords: oxaziridine derivatives; Elastin-like polypeptides; Redox-Activated Chemical Tagging; methionine-containing ELPs

Domains: Polymers; Material chemistry; Biotechnology

Marie Rosselin, Ye Xiao, Ludovic Belhomme, Sébastien Lecommandoux, Elisabeth Garanger. Expanding the Toolbox of Chemoselective Modifications of Protein-Like Polymers at Methionine Residues. ACS Macro Letters, 2019, 8 (12), pp.1648-1653. ⟨10.1021/acsmacrolett.9b00862⟩. ⟨hal-02397850⟩