Cellular thiol groups (Sulfhydryl groups) (-SH)

Cellular thiol groups, or sulfhydryl groups (-SH), are reactive chemical moieties found on cysteine residues within proteins and in low-molecular-weight peptides such as glutathione. In hypoxic environments, these groups become the primary targets for hypoxia-activated prodrugs and diagnostic imaging probes like pimonidazole and fluoromisonidazole (Raleigh et al., 1998). These agents undergo intracellular reduction by enzymes like cytochrome P450 reductase to form reactive intermediates that, in the absence of oxygen, covalently bind to cellular thiols (Koch, 2002). This binding effectively traps the probe within hypoxic cells, allowing for the quantification of tumor hypoxia, which is a key driver of treatment resistance and metastasis (Nordsmark et al., 2005). Furthermore, the interaction with these thiol groups can deplete cellular antioxidant defenses, thereby enhancing the efficacy of radiotherapy and certain chemotherapies. Beyond their role in pharmacology, cellular thiols are essential for maintaining redox homeostasis, protein folding, and signal transduction through the formation of disulfide bonds.

Other names

Sulfhydryl groupsProtein thiolsNon-protein thiolsCysteine residuesGlutathioneNPSH

Hypoxia-selective reductive activation of nitro compounds into reactive species that form covalent adducts with sulfhydryl groups.