Cellular vicinal thiol sites (VTS)

Cellular vicinal thiol sites are functional motifs within proteins characterized by two cysteine residues located in close spatial proximity, enabling them to cycle between reduced dithiol and oxidized disulfide states (PubMed ID: 11062373). These sites play a fundamental role in cellular redox sensing and signaling, acting as molecular switches that regulate the activity of enzymes, transcription factors, and receptors in response to the cellular redox environment (PubMed ID: 15660980). In a therapeutic context, vicinal thiols are highly reactive toward trivalent arsenicals and certain chelating agents, which form stable cyclic structures with the sulfur atoms. A prominent example is the use of arsenic trioxide in treating acute promyelocytic leukemia, where it binds to vicinal thiols in the PML-RARalpha fusion protein to induce its degradation and promote cell differentiation (PubMed ID: 20378816). Beyond oncology, these sites are the primary targets for heavy metal chelators like dimercaprol, which treat poisoning by sequestering metals into stable cyclic complexes (PubChem CID: 10341). However, the widespread distribution of vicinal thiols across numerous essential proteins presents a significant challenge for drug specificity, often leading to off-target toxicity and therapeutic complications.

Other names

Vicinal dithiolsProtein vicinal thiolsVicinal sulfhydryl groupsDithiol motifsRedox-active vicinal cysteines

Drugs typically act by forming stable cyclic dithioarsinite or mercaptide complexes with the two adjacent thiol groups, leading to protein inactivation, conformational changes, or targeted protein degradation.