Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Curr Med Chem. 2021;28(20):3892-3912. doi: 10.2174/0929867327666200810135039.
SUMOylation has emerged as an important post-translational modification that involves the covalent attachment of the Small Ubiquitin-like Modifier (SUMO) polypeptide to a lysine residue of a target protein. The enzymatic pathway of SUMOylation is very similar to ubiquitinylation and involves an activating enzyme, a conjugating enzyme, ligases, and deconjugating enzymes. SUMOylation modulates the function of a number of proteins associated with various pathways, and in fact, dysregulation of the SUMOylation pathway is observed in both cancer and neurological diseases. In many cancers, the SUMO enzymes are upregulated, and SUMO levels correlate directly with prognosis and disease progression. As a result, there has been an emphasis on the discovery and development of inhibitors of SUMOylation. In this review, the latest advances in SUMOylation inhibitors are described alongside the methods used to discover small molecule SUMOylation inhibitors, which include natural products, peptidomimetics, as well as synthetic derivatives identified via virtual screens.
SUMOylation 已成为一种重要的翻译后修饰方式，涉及将小泛素样修饰物（SUMO）多肽共价连接到靶蛋白的赖氨酸残基上。SUMOylation 的酶促途径与泛素化非常相似，涉及激活酶、连接酶、连接酶和去连接酶。SUMOylation 调节与各种途径相关的许多蛋白质的功能，实际上，SUMOylation 途径的失调在癌症和神经疾病中都观察到。在许多癌症中，SUMO 酶上调，SUMO 水平与预后和疾病进展直接相关。因此，人们一直强调发现和开发 SUMOylation 抑制剂。在这篇综述中，描述了 SUMOylation 抑制剂的最新进展，以及发现小分子 SUMOylation 抑制剂的方法，包括天然产物、肽模拟物以及通过虚拟筛选鉴定的合成衍生物。
