{"title":"缩小蛋白质靶向的差距","authors":"Irene Serrano","doi":"10.1038/s41589-024-01766-3","DOIUrl":null,"url":null,"abstract":"","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1387-1387"},"PeriodicalIF":12.9000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bridging the gap in protein targeting\",\"authors\":\"Irene Serrano\",\"doi\":\"10.1038/s41589-024-01766-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\",\"PeriodicalId\":18832,\"journal\":{\"name\":\"Nature chemical biology\",\"volume\":\"20 11\",\"pages\":\"1387-1387\"},\"PeriodicalIF\":12.9000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature chemical biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41589-024-01766-3\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature chemical biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41589-024-01766-3","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
靶向蛋白质降解已成为一种极具前景的治疗方法，可用于调节传统小分子药物难以靶向的蛋白质。最近，这种方法已扩展到改变细胞外蛋白质的水平和活性--包括分泌蛋白和膜蛋白。现在，Zhang 等人利用癌细胞中细胞表面转铁蛋白受体 1（TfR1）的上调及其快速内吞速度，开发出了转铁蛋白受体靶向嵌合体（TransTACs）。研究小组研究了TransTACs消除表面嵌合抗原受体（CAR）的能力。尽管进行了内化，但 CAR 并没有被降解；相反，它被运送到了循环内体。为了解决这个问题，研究小组加入了TfR1抗体粘合剂和Cathepsin B裂解连接体，以促进CAR进入溶酶体降解途径。CAR TransTACs 能有效抑制 Jurkat 和人类原代 CAR T 细胞的活化以及 IFNγ 的分泌。此外，靶标范围还扩大到表皮生长因子受体（EGFR）（用于靶向耐药肺癌）以及 PD-L1 和 CD20，这证明了 TransTACs 能够有效内化和降解结构和功能不同的膜蛋白。
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