Thiol oxidation

Thiol oxidation is a fundamental chemical process in biology whereby thiol groups (–SH) of molecules (notably cysteine residues in proteins or low molecular weight thiols like glutathione) are oxidized by reactive oxygen/nitrogen species (e.g., hydrogen peroxide, peroxynitrite)[2][3][5][6]. The main products include disulfide bonds (between cysteines), sulfenic acid, sulfinic acid, and sulfonic acid, as well as S-glutathionylation[3][5]. This process underlies vital regulatory modifications, notably in redox signaling, antioxidant defense, enzyme activity, and cellular responses to stress. Dysregulated thiol oxidation contributes to diseases such as cancer, cardiovascular diseases, and neurodegeneration[2][4]. Although not a classical drug target, the process is indirectly targeted by antioxidants and redox modulators[2][4][5]. Excessive or irreversible thiol oxidation can lead to protein dysfunction or cell death, posing therapeutic challenges[2][4].

Other names

Protein thiol oxidationCysteine oxidationDisulfide bond formationSulfenylationS-glutathionylationSulfinic/sulfonic acid formation

Antioxidants inhibit thiol oxidation by scavenging oxidants. Redox modulators (e.g., glutathione, thioredoxin) promote reduction and repair of oxidized thiols, restoring protein function. Drugs can promote oxidative stress (pro-oxidants) or inhibit unwanted thiol oxidation to influence cell survival/death.