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Preparation of the Mgm101 Recombination Protein by MBP-based Tagging Strategy
Published on: June 25, 2013
Phosphorescent iridium complexes activated by endogenous zinc as a mitochondrial DNA nuclease for stimulation of the
Zhi-Yuan Li1,2, Long-Bo Yu1,2, Qing-Hua Shen1,2
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University Guangzhou 510006 China lingyy@gdmu.edu.cn tancaip@mail.sysu.edu.cn.
Abstract:
Zinc is a crucial element in cellular processes, and its homeostasis has intricate relationships with the initiation, progression, and therapeutic intervention of cancer. Activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been proven to be an effective strategy for cancer immunotherapy. Herein, we report four phosphorescent iridium complexes (Ir1-Ir4) with zinc chelating ligands. Among them, Ir1 can bind and image mitochondrial chelatable zinc ions via phosphorescence-lifetime responses, consequently modulating the expression of zinc-regulatory proteins. Furthermore, the in situ formed heteronuclear metal complex Ir1-Zn2 shows nuclease mimetic activities, capable of hydrolyzing mitochondrial DNA (mtDNA) to release mtDNA fragments for the activation of the cGAS-STING pathway. In conclusion, we designed a mitochondria-targeting phosphorescent Ir(iii) complex with dual functions in dysregulation of zinc homeostasis and generation of nuclease in situ, which provides an innovative approach to stimulate the cGAS-STING pathway.
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