Squaryl group-modified UDP analogs as inhibitors of the endoplasmic reticulum-resident folding sensor enzyme UGGT
Squaryl group-modified UDP analogs as inhibitors of the endoplasmic reticulum-resident folding sensor enzyme UGGT
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DOI：
10.1039/d2cc06634c
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发表时间：
2023-01-31
影响因子：
4.9
通讯作者：
Ito, Yukishige
中科院分区：
文献类型：
--
作者：
Abe, Junpei;Takeda, Yoichi;Ito, Yukishige
UDP-Glc：糖蛋白葡糖基转移酶（UGGT）在维持内质网（ER）中正确折叠的N-糖蛋白的质量控制方面具有核心作用。选择性和有效的UGGT抑制剂可能导致UGGT相关事件的阐明，但这样的分子尚未确定到目前为止。具有UGGT抑制活性的小分子的实例很少。在这里，我们报告方芳基基团修饰的UDP类似物作为一个有前途的UGGT抑制剂。其中，具有尿苷部分的2 '-氨基和羟乙基取代的方酰胺的化合物表现出最高的效力，表明其作为进一步优化的分子的相关性。
UDP-Glc:glycoprotein glucosyltransferase (UGGT) has a central role to retain quality control of correctly folded N-glycoprotein in the endoplasmic reticulum (ER). A selective and potent inhibitor against UGGT could lead to elucidation of UGGT-related events, but such a molecule has not been identified so far. Examples of small molecules with UGGT inhibitory activity are scarce. Here, we report squaryl group-modified UDP analogs as a promising UGGT inhibitor. Among these, the compound possessing a 2 '-amino group of the uridine moiety and hydroxyethyl-substituted squaramide exhibited the highest potency, suggesting its relevance as a molecule for further optimization.