CIIL, Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, UMR 9017, 59000, Lille, France.
XProChem, 70 Rue du Dr. Yersin, 59120, Loos, France.
Angew Chem Int Ed Engl. 2023 Apr 24;62(18):e202302648. doi: 10.1002/anie.202302648. Epub 2023 Mar 28.
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.
基于连接化学在半胱氨酸应用的蛋白质化学合成的一个支柱是一组反应，这些反应能够选择性地将半胱氨酸残基脱硫成丙氨酸。现代脱硫反应使用膦作为硫的汇，在涉及生成硫中心自由基的激活条件下。在这里，我们表明，在碳酸氢盐缓冲液中，在有氧条件下，铁可以在微摩尔浓度下有效地进行半胱氨酸脱硫，这是使用类似于天然水中发生的铁催化氧化现象的条件。因此，我们的工作表明，在水生系统中发生的化学过程可以被适应于化学反应器，以触发蛋白质水平上的复杂化学选择性转化，同时最大限度地减少对有害化学物质的依赖。
