Brackett Christopher M, García-Casas Ana, Castillo-Lluva Sonia, Blagg Brian S J
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Biológicas, Universidad Complutense, Madrid 28040, España.
ACS Med Chem Lett. 2020 Sep 24;11(11):2221-2226. doi: 10.1021/acsmedchemlett.0c00353. eCollection 2020 Nov 12.
SUMOylation has emerged as an important post-translational modification that has been shown to modulate protein activity associated with various signaling pathways, and consequently, it has emerged as an important therapeutic target. While several natural products have been shown to inhibit enzymes involved in the SUMOylation process, there has been little progress toward the development of more selective and potent SUMOylation inhibitors. Ginkgolic acid was one of the first natural products discovered to inhibit the SUMO E1 enzyme. Despite its use to mechanistically investigate the SUMOylation process, ginkgolic acid also modulates other pathways as well. In this Letter, preliminary structure-activity relationships for ginkgolic acid as a SUMOylation inhibitor are presented.
SUMO化已成为一种重要的翻译后修饰，已被证明可调节与各种信号通路相关的蛋白质活性，因此，它已成为一个重要的治疗靶点。虽然几种天然产物已被证明可抑制参与SUMO化过程的酶，但在开发更具选择性和强效的SUMO化抑制剂方面进展甚微。银杏酸是最早发现的抑制SUMO E1酶的天然产物之一。尽管它被用于从机制上研究SUMO化过程，但银杏酸也会调节其他通路。在本信函中，展示了银杏酸作为SUMO化抑制剂的初步构效关系。
