Harinath Chakrapani
Indian Institute of Science Education and Research, Pune, India
Redox Chemical Biology Tools to Modulate Biochalcogen Transfer
Maintenance of reducing and oxidizing equivalents is fundamental to cellular survival and growth. In addition to nitrogen and oxygen, biochalcogens, sulfur and selenium,(1,2) are vital contributors to redox homeostasis. For example, hydrogen sulfide (H2S) is synthesized in cells, is a key mediator of antioxidant response, and is involved in host-pathogen interactions.(1) Hence, modulation of sulfur transfer within cells in a controlled manner is essential to better understand these complex processes. Our lab develops cell-permeable tools that mediate sulfur transfer. We designed artificial substrates for 3-mercaptopyruvate sulfurtransferase (3-MST),(3) a key enzyme involved in sulfur trafficking, H2S biosynthesis, and antioxidant response.(4) Using these tools, we study cell-specific as well as organelle-specific sulfur transfer in the context of stress response.(5) We also find that this strategy is useful in protecting cells from ferroptosis, a form of cell death that is increasing associated with degenerative diseases.(6) Lastly, we present a new tool to generate hydrogen selenide (H2Se),(7) a key intermediate in the biosynthesis of selenoproteins, which are major antioxidant enzymes in cells.7 Collectively, the high precision tools enable us to interrogate redox biology of health and disease and have wide-ranging applications.
References
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2. Cupp-Sutton, K.; Ashby, M. Antioxidants 2016, 5, 42. (b) Kim, D. and coworkers Nat. Metab. 2024, 6, 343–358.
3. Pedre, B.; Talwar, D.; Barayeu, U.; Schilling, D.; Luzarowski, M.; Sokolowski, M.; Glatt, S.; Dick, T. P. Nat. Chem. Biol. 2023, 19 (4), 507–517.
4. Bora, P.; Manna, S.; Nair, M.; Sathe, R.M.S.; Singh, S.; Adury, V.S.S.; Gupta, K.; Mukherjee, A.; Saini, D. K.; Kamat, S.S.; Hazra, A. B.; Chakrapani, H. Chem. Sci., 2021, 12, 12939-12949. (b) Gupta, S. M.; Mohite, P. S. Chakrapani, H. Chem. Sci. 2025, 16, 4695-4702. (c) Manna, S.; Gupta, S. M.; Bora, P.; Chakraborty, A.; Anand Kumar, T.; Kamat, S.S.; Chakrapani, H. Angew. Chem. Intl Ed. 2025, 64, e202502917.
5. Manna, S.; Agrawal, R.; Yadav, T. Anand Kumar, T.; Kumari, P. Dalai, A.; Kanade, S. Balasubramanian, N. Singh, A.; Chakrapani, H. Angew. Chem. Intl Ed. 2024, 63, e202411133
6. Chakrapani, H. and coworkers, manuscript under revision.
7. Dey Sarkar, U.; Rana, M.; Chakrapani, H. Chem. Sci. 2024, 15, 19315-19321 (b) Chakrapani, H. and coworkers, manuscript under preparation