Liu Jiamei, Wei Tongyao, Tan Yi, Liu Heng, Li Xuechen
Department of Chemistry, State Key Lab of Synthetic Chemistry, The University of Hong Kong Hong Kong
Chem Sci. 2021 Dec 28;13(5):1367-1374. doi: 10.1039/d1sc06387a. eCollection 2022 Feb 2.
Chemical synthesis of proteins with poor solubility presents a challenging task. The existing solubilizing tag strategies are not suitable for the expressed protein segment. To address this issue, we report herein that solubilizing tags could be introduced at the side chain of the peptide and C-terminal peptide salicylaldehyde esters a disulfide linker. Such reducible solubilizing tags (RSTs) are compatible with peptide salicylaldehyde ester-mediated Ser/Thr ligation and Cys/Pen ligation for purifying and ligating peptides with poor solubility. This strategy features operational simplicity and readily accessible materials. Both the protein 2B4 cytoplasmic tail and FCER1G protein have been successfully synthesized this strategy. Of particular note, the RST strategy could be used for solubilizing the expressed protein segment for protein semi-synthesis of the HMGB1 protein.
对溶解性差的蛋白质进行化学合成是一项具有挑战性的任务。现有的增溶标签策略不适用于表达的蛋白质片段。为了解决这个问题，我们在此报告，可以在肽的侧链引入增溶标签以及C端肽水杨醛酯——一种二硫键连接子。这种可还原增溶标签（RST）与肽水杨醛酯介导的丝氨酸/苏氨酸连接和半胱氨酸/青霉胺连接兼容，用于纯化和连接溶解性差的肽。该策略具有操作简单和材料易于获取的特点。蛋白质2B4细胞质尾段和FCER1G蛋白均已通过此策略成功合成。特别值得注意的是，RST策略可用于增溶表达的蛋白质片段，以进行HMGB1蛋白的蛋白质半合成。
