Cellular thiol-containing proteins and small-molecule thiols

Cellular thiol-containing proteins and small-molecule thiols constitute a vital chemical network responsible for maintaining the redox environment of the cell. Small-molecule thiols, primarily glutathione (GSH), act as the first line of defense against oxidative damage and electrophilic stress by neutralizing reactive oxygen species and detoxifying xenobiotics [1]. Thiol-containing proteins, such as thioredoxin and various metabolic enzymes, utilize the reactivity of the cysteine sulfhydryl group for catalytic activity and redox-sensitive signaling [2]. In pathological states like cancer, elevated thiol levels often contribute to drug resistance, while in neurodegenerative diseases, thiol depletion is linked to oxidative damage [3]. Therapeutic strategies often involve the use of electrophilic agents or metal-based drugs, such as cisplatin or auranofin, which form stable adducts with these thiol groups to disrupt cellular function and induce apoptosis [4]. Because thiols are ubiquitous and essential for normal physiology, targeting them generally presents significant challenges regarding selectivity and systemic safety [5]. The collective of these molecules is often referred to as the "thiolome," and its modulation is a key area of research in redox pharmacology [5].

Other names

ThiolomeCellular thiol poolSulfhydryl-containing moleculesProtein and non-protein thiolsReactive thiolome

Drugs targeting this group typically act through the covalent modification of sulfhydryl (-SH) groups, leading to the irreversible or reversible inhibition of thiol-dependent enzymes, the depletion of the cellular antioxidant pool (e.g., glutathione), or the induction of oxidative stress [4, 5].