Vicinal-thiol–containing proteins (VTPs)

Vicinal-thiol–containing proteins (VTPs) are a diverse class of proteins characterized by the presence of two or more cysteine residues in close spatial proximity, which allows them to form stable, covalent cyclic dithioarsinite complexes with trivalent arsenicals (Source: BenchChem, ResearchGate). These proteins play fundamental roles in cellular metabolism and regulation, most notably as essential components of alpha-keto acid dehydrogenase complexes, such as pyruvate dehydrogenase, and as key players in redox signaling, including thioredoxins and protein tyrosine phosphatases (Source: World Scientific, NIH). In clinical oncology, VTPs are recognized as secondary targets of arsenic trioxide (Trisenox), where their inhibition complements the degradation of the primary target, the PML-RAR alpha fusion protein, to induce apoptosis in acute promyelocytic leukemia cells (Source: FDA Label for Trisenox). Beyond cancer, VTPs are also targeted by drugs like melarsoprol for the treatment of African trypanosomiasis, exploiting the high sensitivity of parasitic enzymes to arsenic binding (Source: JBIC Journal of Biological Inorganic Chemistry). However, because vicinal thiol groups are ubiquitous across many critical human enzymes and receptors, their non-specific modification by arsenicals is a primary driver of systemic toxicity, including neurotoxicity, hepatotoxicity, and cardiovascular complications (Source: ResearchGate). Consequently, VTPs represent a complex therapeutic landscape where the same chemical reactivity that enables drug efficacy also necessitates careful management of off-target safety risks.

Other names

Vicinal-thiol proteinsVTPsDithiol-containing proteinsArsenic-binding proteinsVicinal dithiols

Trivalent arsenicals bind covalently to vicinal (closely spaced) sulfhydryl groups on cysteine residues, forming stable cyclic dithioarsinite structures that inhibit enzymatic activity or induce conformational changes in the target proteins (Source: BenchChem, FDA).