In Situ Assembly of Platinum(II)-Metallopeptide Nanostructures Disrupts Energy Homeostasis and Cellular Metabolism

作者：Zhixuan Zhou, Konrad Maxeiner, Pierpaolo Moscariello, Si-Yuan Xiang, Yingke Wu, Yong Ren, Colette J. Whitfield, Lujuan Xu, A. Kaltbeitzel, Shen Han, David Mücke, Haoyuan Qi, M. Wagner, Ute Kaiser, K. Landfester, I. Lieberwirth, D. Ng, T. Weil · 发表于：Journal of the American Chemical Society · 年份：2022 · DOI：10.1021/jacs.2c03215 · 被引用次数：42 · 研究领域：Medicine

Nanostructure-based functions are omnipresent in nature and essential for the diversity of life. Unlike small molecules, which are often inhibitors of enzymes or biomimetics with established methods of elucidation, we show that functions of nanoscale structures in cells are complex and can implicate system-level effects such as the regulation of energy and redox homeostasis. Herein, we design a platinum(II)-containing tripeptide that assembles into intracellular fibrillar nanostructures upon molecular rearrangement in the presence of endogenous H2O2. The formed nanostructures blocked metabolic functions, including aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. As a consequence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated. We demonstrate that assembly-driven nanomaterials offer a rich avenue to achieve broad-spectrum bioactivities that could provide new opportunities in drug discovery.