Intracellular thiol-containing proteins

Intracellular thiol-containing proteins are a broad class of proteins that possess reactive sulfhydryl (-SH) groups, primarily on cysteine residues, which are essential for maintaining cellular redox homeostasis and signaling (Source: PubMed, PMID: 22611156). These proteins, including thioredoxins and glutaredoxins, act as critical antioxidants and molecular switches that respond to oxidative stress by undergoing reversible modifications like glutathionylation or disulfide bond formation (Source: NIH, PMC3521968). In various diseases, such as cancer and neurodegenerative disorders, the dysregulation of these thiol-based systems contributes to pathological progression by altering protein folding and enzymatic activities (Source: Nature Reviews Drug Discovery). Many drugs, including electrophilic agents like dimethyl fumarate and certain chemotherapeutics like cisplatin, interact with these proteins through covalent binding or by inducing oxidative modifications (Source: PubChem). However, because these proteins are ubiquitous, targeting them often presents challenges related to off-target effects and systemic toxicity (Source: StatPearls).

Other names

Protein thiolsSulfhydryl-containing proteinsIntracellular thiolsCysteine-rich proteins

Drugs interact with these proteins primarily through covalent modification of the nucleophilic sulfhydryl (-SH) group of cysteine residues, which can modulate protein function, activate redox-sensitive transcription factors like Nrf2, or deplete cellular antioxidant capacity (Source: PubMed, PMID: 22611156).