Site-selective protein modification strategies can be used to insert non-natural functional groups into protein structures. Herein, we report on the use of the bis-electrophile 3-bromo-2-bromomethyl-1-propene as a reagent to introduce an electrophilic handle at cysteine residues under mild conditions. This method is demonstrated on a variety of proteins containing a solvent-exposed cysteine residue, including an anti-HER2 nanobody. Chemically distinct protein conjugates are then efficiently formed through further reaction of the electrophilic site with various nucleophiles, including thiols and amines. The resulting chemically-defined conjugates are highly stable in the presence of glutathione or human plasma and retain both the structure and function of the native protein.

位点选择性蛋白质修饰策略可用于将非天然官能团插入蛋白质结构中。在本文中，我们报道了在温和条件下使用双亲电子试剂3-bromo-2-bromomethyl-1-propene作为试剂在半胱氨酸残基上引入亲电试剂的方法。该方法在多种含有溶剂暴露的半胱氨酸残基的蛋白质上得到了证明，包括抗HER2纳米抗体。然后，通过亲电子位点与各种亲核试剂（包括硫醇和胺）的进一步反应，可以有效地形成化学上不同的蛋白质偶联物。在谷胱甘肽或人血浆存在下，所得的化学确定的缀合物高度稳定，并且保留天然蛋白质的结构和功能。