Cellular thiols and proteins

Cellular thiols and proteins represent a broad and heterogeneous class of molecules defined by the presence of reactive sulfhydryl (-SH) groups, which are essential for maintaining the cellular redox environment and protein functionality (Circu & Aw, 2010, Free Radic. Biol. Med.). This category includes low-molecular-weight antioxidants like glutathione (GSH) and a vast array of proteins where cysteine residues serve as catalytic centers or structural stabilizers (Pompella et al., 2003, Ital. J. Biochem.). In a pharmacological context, these molecules are often targeted by electrophilic agents, heavy metals, and reactive drug metabolites that form covalent adducts with sulfur atoms, potentially leading to enzyme inhibition or the depletion of antioxidant defenses (Kalinina et al., 2014, Curr. Med. Chem.). For example, platinum-based chemotherapeutics like cisplatin and gold-based compounds like auranofin interact with these thiol groups to exert their cytotoxic or anti-inflammatory effects (Casini et al., 2008, J. Biol. Inorg. Chem.). While modulating cellular thiols can be a potent therapeutic strategy for treating cancer or oxidative stress, the inherent lack of specificity poses significant risks, including off-target toxicity and the impairment of essential cellular signaling pathways (Hansen et al., 2009, Free Radic. Biol. Med.).

Other names

Intracellular thiolsProtein sulfhydrylsThiol-containing moleculesSulfhydryl groupsProtein thiols

Drugs interact with cellular thiols and proteins primarily through covalent modification (alkylation, arylation, or metal-coordination) of sulfhydryl groups, which can deplete glutathione levels, inhibit redox-sensitive enzymes, or trigger the Nrf2-mediated antioxidant response (Kalinina et al., 2014, Curr. Med. Chem.).