An Iron‐Catalyzed Protein Desulfurization Method Reminiscent of Aquatic Chemistry. Issue 18 (28th March 2023)

• Record Type: Journal Article
• Authors: Desmet, Rémi; Boidin‐Wichlacz, Céline; Mhidia, Reda; Tasiemski, Aurélie; Agouridas, Vangelis; Melnyk, Oleg
• Is Part Of: Angewandte Chemie international edition. Volume 62:Issue 18(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-28
• Subjects: Aquatic Chemistry -- Carbonate -- Desulfurization -- Iron -- Protein; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202302648
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: One pillar of protein chemical synthesis based on the application of ligation chemistries to cysteine is the group of reactions enabling the selective desulfurization of cysteine residues into alanines. Modern desulfurization reactions use a phosphine as a sink for sulfur under activation conditions involving the generation of sulfur‐centered radicals. Here we show that cysteine desulfurization by a phosphine can be effected efficiently by micromolar concentrations of iron under aerobic conditions in hydrogen carbonate buffer, that is using conditions that are reminiscent of iron‐catalyzed oxidation phenomena occurring in natural waters. Therefore, our work shows that chemical processes taking place in aquatic systems can be adapted to a chemical reactor for triggering a complex chemoselective transformation at the protein level, while minimizing the resort to harmful chemicals. Abstract : Cysteine desulfurization by a phosphine can be efficiently achieved under aerobic conditions in hydrogen carbonate buffer by micromolar concentrations of iron. The desulfurization mechanism likely involves iron(III) species produced through the oxidation of iron(II)‐carbonate complexes by molecular oxygen and is reminiscent of iron‐catalyzed oxidation phenomena occurring in natural waters.