Enzymatically Formed Peptide Assemblies Sequestrate Proteins and Relocate Inhibitors to Selectively Kill Cancer Cells.,Angewandte Chemie International Edition

当前位置： X-MOL 学术 › Angew. Chem. Int. Ed. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Enzymatically Formed Peptide Assemblies Sequestrate Proteins and Relocate Inhibitors to Selectively Kill Cancer Cells.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-06-10 , DOI: 10.1002/anie.202006290
Hongjian He ₁ , Shuang Liu ₁ , Difei Wu ₁ , Bing Xu ₁

Affiliation

Herein, we show that an enzymatic reaction can generate peptide assemblies that sequestrate proteins to selectively kill cancer cells. A phosphopeptide bearing the antagonistic motif (AVPI) to the inhibitors of apoptotic proteins (IAPs) enters cancer cells and normal cells by caveolin‐dependent endocytosis and macropinocytosis, respectively. The AVPI‐bearing peptide assemblies sequestrates IAPs and releases bortezomib (BTZ), a proteasome inhibitor, in the cytosol of cancer cells, but rescues the normal cells (namely, HS‐5 cells) by trafficking the BTZ into lysosomes. Alkaline phosphatase (ALP) acts as a context‐dependent signal for trafficking the peptide/BTZ assemblies and selectively induces the death of the cancer cells. The assemblies of AVPI exhibit enhanced proteolytic resistance. This work, which utilizes the difference in endocytic uptake of enzymatically formed peptide assemblies to selectively kill cancer cells, promises a new way to develop selective cancer therapeutics.

中文翻译：

酶促形成的肽组装体隔离蛋白质并重新定位抑制剂以选择性杀死癌细胞。

在此，我们证明酶促反应可以产生肽组装体，该肽组装体隔离蛋白质以选择性杀死癌细胞。带有凋亡蛋白抑制剂（IAP）拮抗基序（AVPI）的磷酸肽分别通过小窝蛋白依赖性内吞作用和巨胞饮作用进入癌细胞和正常细胞。带有 AVPI 的肽组装体隔离 IAP 并在癌细胞的细胞质中释放硼替佐米 (BTZ)（一种蛋白酶体抑制剂），但通过将 BTZ 运输到溶酶体中来拯救正常细胞（即 HS-5 细胞）。碱性磷酸酶 (ALP) 作为肽/BTZ 组装体运输的环境依赖性信号，并选择性诱导癌细胞死亡。AVPI 的组装体表现出增强的蛋白水解抗性。这项工作利用酶促形成的肽组装体的内吞摄取差异来选择性杀死癌细胞，为开发选择性癌症疗法提供了一种新方法。

更新日期：2020-06-10

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南