Cellular cysteine-containing proteins and peptides

Cellular cysteine-containing proteins and peptides represent a diverse group of intracellular molecules that contain the nucleophilic amino acid cysteine. This category encompasses small antioxidant peptides like glutathione (GSH) as well as a vast array of functional proteins where cysteine residues are vital for enzymatic catalysis, structural stability, and metal binding [PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659252/]. These molecules play a fundamental role in maintaining the cell's redox environment and protecting against oxidative stress by neutralizing reactive oxygen and nitrogen species [PubMed: https://pubmed.ncbi.nlm.nih.gov/23517018/]. In clinical pharmacology, this group is a primary site of interaction for electrophilic drugs, including platinum-based chemotherapeutics like cisplatin and various covalent inhibitors [DrugBank: https://go.drugbank.com/drugs/DB00515]. While some drugs are designed to target specific cysteines in proteins like BTK or EGFR, the broader pool of cellular thiols often acts as a scavenger, impacting the drug's pharmacokinetics and toxicity profile [Nature: https://www.nature.com/articles/nrd3299]. Depletion of these cellular thiols can lead to increased oxidative damage, mitochondrial dysfunction, and the activation of apoptotic pathways [PubMed: https://pubmed.ncbi.nlm.nih.gov/11356661/]. Furthermore, alterations in the expression or reactivity of these proteins are frequently associated with the development of drug resistance in cancer therapy [PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688034/].

Other names

Cellular thiolsProtein thiolsCysteine-rich proteinsThiol-containing peptidesIntracellular sulfhydryl groups

Drugs interact with this target through the formation of covalent bonds or coordination complexes with the nucleophilic sulfhydryl (-SH) group of cysteine residues, leading to protein modification, enzyme inhibition, or depletion of cellular antioxidant capacity [DrugBank: https://go.drugbank.com/drugs/DB00515; Nature Reviews Drug Discovery: https://www.nature.com/articles/nrd3299].