Carbon Monoxide in Drug Discovery by Binghe Wang & Leo E. Otterbein

Carbon Monoxide in Drug Discovery by Binghe Wang & Leo E. Otterbein

Author:Binghe Wang & Leo E. Otterbein [Wang, Binghe & E. Otterbein, Leo]
Language: eng
Format: epub
Published: 2022-04-27T18:39:14+00:00


Thiol Sensing

Increased levels of GSH, cysteine, and other intracellular thiols in the environment of cancer cells have been used as triggers to induce release of drug molecules, including CO [101]. To enable thiol sensing prior to visible light-triggered CO release, the extended flavonol 30 was functionalized with a Michael acceptor to give 39 (Figure 15.10). Solution and cell-based studies demonstrate logic gate-type deprotection reactivity with cysteine, with distinct fluorescence signals evident for 39 and 30, which enabled sensing of endogenous cellular thiols prior to triggered CO release. Notably, while the latter step involves dioxygenase-type CO release reactivity from 30, the reaction proceeds under hypoxic (1% O2) conditions [100].



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