The T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immunoreceptor expressed on lymphocytes that serves as a promising target for cancer immunotherapy. In this study, facile synthetic protocols to produce the extracellular domain of TIGIT were investigated for applications of TIGIT in mirror-image screening. During the synthesis via sequential native chemical ligations, we encountered problems with significantly poor solubility of the ligated products. Introducing trityl-type solubilizing auxiliaries, which also functioned as temporary protecting groups for cysteine residues, facilitated a flexible order of ligations and efficient purification protocols. After refolding under appropriate conditions, the synthetic TIGIT showed a sufficient affinity toward its target ligand CD155.

具有免疫球蛋白和免疫受体酪氨酸抑制基序结构域 (TIGIT) 的 T 细胞免疫受体是一种在淋巴细胞上表达的抑制性免疫受体，可作为癌症免疫治疗的有希望的靶点。在本研究中，研究了产生 TIGIT 胞外结构域的简便合成方案，以用于 TIGIT 在镜像筛选中的应用。在通过连续天然化学连接进行合成的过程中，我们遇到了连接产物溶解度明显较差的问题。引入三苯甲基型增溶助剂，也可作为半胱氨酸残基的临时保护基团，有利于灵活的连接顺序和高效的纯化方案。在适当的条件下重折叠后，合成的TIGIT对其靶配体CD155表现出足够的亲和力。