Peiran Zhao, Huiyan Li, Bingxia Sun, Chaochao Wang, Guanglei Lv, Chao Chen, Leilei Ying, Xinhong He, Dayong Jin, Wenbo Bu
Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R∙) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R∙ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R∙. At a temperature of 43°C, the generated R∙ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction...
April 29, 2024: Angewandte Chemie