Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, P.O. Box 100485, Gainesville, Florida 32610, USA.
Nat Prod Rep. 2020 May 1;37(5):717-736. doi: 10.1039/c9np00066f. Epub 2020 Feb 18.
Covering: up to the end of 2019Diverse natural product small molecules have allowed critical insights into processes that govern eukaryotic cells' ability to secrete cytosolically synthesized secretory proteins into their surroundings or to insert newly synthesized integral membrane proteins into the lipid bilayer of the endoplasmic reticulum. In addition, many components of the endoplasmic reticulum, required for protein homeostasis or other processes such as lipid metabolism or maintenance of calcium homeostasis, are being investigated for their potential in modulating human disease conditions such as cancer, neurodegenerative conditions and diabetes. In this review, we cover recent findings up to the end of 2019 on natural products that influence protein secretion or impact ER protein homeostasis, and serve as powerful chemical tools to understand protein flux through the mammalian secretory pathway and as leads for the discovery of new therapeutics.
截至 2019 年底 多种多样的天然产物小分子使人们能够深入了解控制真核细胞将细胞质中合成的分泌蛋白分泌到周围环境或将新合成的完整膜蛋白插入内质网膜脂质双层的过程。此外,正在研究内质网的许多成分,这些成分对于蛋白质的动态平衡或其他过程(如脂质代谢或钙动态平衡的维持)是必需的,以研究它们在调节人类疾病(如癌症、神经退行性疾病和糖尿病)方面的潜力。在这篇综述中,我们涵盖了截至 2019 年底关于影响蛋白质分泌或影响内质网蛋白质动态平衡的天然产物的最新发现,并作为强大的化学工具,用于理解蛋白质通过哺乳动物分泌途径的通量,并作为发现新疗法的先导。