Targeting protein lipidation in disease.

Targeting protein lipidation in disease.
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靶向疾病中的蛋白质脂化。

DOI:
10.1016/j.molmed.2012.01.007
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发表时间:
2012-04
影响因子:
13.6
通讯作者:
Resh MD
Resh MD
中科院分区:
医学1区
文献类型:
--
作者:
Resh MD

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脂肪酸和/或类异戊二烯共价连接到多种疾病相关蛋白质。这些疏水部分的独特化学性质使得脂质修饰能够作为调节蛋白质结构、定位和功能的机制。这篇综述重点介绍了在鉴定蛋白质脂化抑制剂及其对人类疾病的影响方面的最新进展。肉豆蔻酰化抑制剂已显示出阻断人类病原体作用的前景。尽管阻断 Ras 蛋白异戊二烯化的抑制剂尚未成功用于癌症治疗,但它们可能对罕见的早衰综合征有效。最近发现了改变 Ras、Wnt 和 Hh 蛋白棕榈酰化状态的药物,它们代表了下一代潜在的化疗药物。
Fatty acids and/or isoprenoids are covalently attached to a variety of disease-related proteins. The distinct chemical properties of each of these hydrophobic moieties allow lipid modification to serve as a mechanism to regulate protein structure, localization and function. This review highlights recent progress in identifying inhibitors of protein lipidation and their effects on human disease. Myristoylation inhibitors have shown promise in blocking the action of human pathogens. Although inhibitors that block prenylation of Ras proteins have not yet been successful for cancer treatment, they may be efficacious in the rare premature aging syndrome progeria. Agents that alter the palmitoylation status of Ras, Wnt and Hh proteins have recently been discovered, and represent the next generation of potential chemotherapeutics.
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