Chemical synthesis of proteins with aggregable or colloidal peptide segments presents a formidable task, as such peptides prove to be difficult for both solid-phase peptide synthesis and peptide ligation. To address this issue, we have developed ligation embedding aggregation disruptor (LEAD) as an effective strategy for the chemical synthesis of difficult-to-obtain proteins. The N,O/S-benzylidene acetals generated from Ser/Thr ligation and Cys/Pen ligation are found to effectively disrupt peptide aggregation, and they can be carried for sequential ligations toward protein synthesis. The effectiveness and generality of this strategy have been demonstrated with total syntheses of programmed cell death protein 1 immunoglobulin like V-type domain and extracellular domain.

中文翻译：

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连接嵌入聚合破坏策略使 PD-1 免疫球蛋白和细胞外结构域的化学合成成为可能

具有可聚集或胶体肽段的蛋白质的化学合成提出了一项艰巨的任务，因为这种肽被证明对于固相肽合成和肽连接都是困难的。为了解决这个问题，我们开发了连接嵌入聚合破坏剂 (LEAD) 作为化学合成难以获得的蛋白质的有效策略。N , O / S _发现由 Ser/Thr 连接和 Cys/Pen 连接产生的 - 亚苄基缩醛可有效破坏肽聚集，并且可用于蛋白质合成的连续连接。该策略的有效性和普遍性已通过程序性细胞死亡蛋白 1 免疫球蛋白（如 V 型结构域和细胞外结构域）的全合成得到证明。