Open AccessIn Situ Assembly of Platinum(II)-Metallopeptide Nanostructures Disrupts Energy Homeostasis and Cellular Metabolism
Author(s) -
Zhixuan Zhou,
Konrad Maxeiner,
Pierpaolo Moscariello,
Siyuan Xiang,
Yingke Wu,
Yong Ren,
Colette J. Whitfield,
Lujuan Xu,
Anke Kaltbeitzel,
Shen Han,
David Mücke,
Haoyuan Qi,
Manfred Wagner,
Ute Kaiser,
Katharina Landfester,
Ingo Lieberwirth,
David Y. W. Ng,
Tanja Weil
Publication year - 2022
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.2c03215
Subject(s) - chemistry , biochemistry , microbiology and biotechnology , small molecule , biophysics , nanotechnology , biology , materials science
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 H 2 O 2 . 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.