Enzymatic Assemblies of Thiophosphopeptides Instantly Target Golgi Apparatus and Selectively Kill Cancer Cells**,Angewandte Chemie International Edition

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Enzymatic Assemblies of Thiophosphopeptides Instantly Target Golgi Apparatus and Selectively Kill Cancer Cells**
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2021-03-30 , DOI: 10.1002/anie.202102601
Weiyi Tan ₁ , Qiuxin Zhang ₁ , Jiaqing Wang ₁ , Meihui Yi ₁ , Hongjian He ₁ , Bing Xu ₁

Affiliation

Changing an oxygen atom of the phosphoester bond in phosphopeptides by a sulfur atom enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells by enzymatic self-assembly. Specifically, conjugating cysteamine S-phosphate to the C-terminal of a self-assembling peptide generates a thiophosphopeptide. Being a substrate of alkaline phosphatase (ALP), the thiophosphopeptide undergoes rapid ALP-catalyzed dephosphorylation to form a thiopeptide that self-assembles. The thiophosphopeptide enters cells via caveolin-mediated endocytosis and macropinocytosis and instantly accumulates in GA because of dephosphorylation and formation of disulfide bonds in Golgi by themselves and with Golgi proteins. Moreover, the thiophosphopeptide potently and selectively inhibits cancer cells (HeLa) with the IC₅₀ (about 3 μM), which is an order of magnitude more potent than that of the parent phosphopeptide.

中文翻译：

硫代磷酸肽的酶促组装立即靶向高尔基体并选择性杀死癌细胞**

用硫原子改变磷酸肽中磷酸酯键的氧原子，可以立即靶向高尔基体 (GA)，并通过酶促自组装选择性杀死癌细胞。具体来说，将半胱胺 S-磷酸与自组装肽的 C 末端缀合会生成硫代磷酸肽。作为碱性磷酸酶 (ALP) 的底物，硫代磷酸肽经历 ALP 催化的快速去磷酸化，形成自组装的硫肽。硫代磷酸肽通过小窝蛋白介导的内吞作用和巨胞饮作用进入细胞，并由于自身和高尔基体蛋白的去磷酸化和在高尔基体中形成二硫键而立即在 GA 中积累。此外，硫代磷酸肽可有效、选择性地抑制癌细胞 (HeLa)，IC ₅₀（约 3 μM），比母体磷酸肽强一个数量级。

更新日期：2021-05-26

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