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Yang Sung Sohn Anat losub-Amir Alfredo E. Cardenas Ola Karmi Merav Darash Yahana Tal Gruman Linda Rowland Henri-Baptiste Marjault Lauren J. Webb Ron Mittler Ron Elber Assaf Friedler Rachel Nechushtai 《Chemical science》2022,13(23):6929
An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-144-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-144-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. 相似文献
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Dr. Guo-Feng Luo Yonatan Biniuri Dr. Wei-Hai Chen Dr. Jianbang Wang Ehud Neumann Henri-Baptiste Marjault Prof. Rachel Nechushtai Dr. Martin Winkler Prof. Thomas Happe Prof. Itamar Willner 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(23):9248-9255
All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII-protoporphyrin IX (ZnIIPPIX)-functionalized G-quadruplex conjugated to the 3′- or 5′-end of the tyrosinamide (TA) aptamer and ZnIIPPIX/G-quadruplex linked to the 3′- and 5′-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from ZnIIPPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV2+, bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnIIPPIX/G-quadruplex by TA-MV2+ controls the efficiency of the generation of TA-MV+.. The photosystem-controlled formation of TA-MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin-NADP+ reductase (FNR)-catalysed reduction of NADP+ to NADPH by TA-MV+., and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1-phenylethanol by NADPH. 相似文献
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Guo‐Feng Luo Yonatan Biniuri Wei‐Hai Chen Jianbang Wang Ehud Neumann Henri‐Baptiste Marjault Rachel Nechushtai Martin Winkler Thomas Happe Itamar Willner 《Angewandte Chemie (International ed. in English)》2020,59(23):9163-9170
All‐DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII‐protoporphyrin IX (ZnIIPPIX)‐functionalized G‐quadruplex conjugated to the 3′‐ or 5′‐end of the tyrosinamide (TA) aptamer and ZnIIPPIX/G‐quadruplex linked to the 3′‐ and 5′‐ends of the TA aptamer through a four‐thymidine bridge. Effective photoinduced electron transfer (ET) from ZnIIPPIX/G‐quadruplex to bipyridinium‐functionalized tyrosinamide, TA‐MV2+, bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnIIPPIX/G‐quadruplex by TA‐MV2+ controls the efficiency of the generation of TA‐MV+.. The photosystem‐controlled formation of TA‐MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin‐NADP+ reductase (FNR)‐catalysed reduction of NADP+ to NADPH by TA‐MV+., and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1‐phenylethanol by NADPH. 相似文献
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