Enhanced Toxicity of the Protein Cross-Linkers Divinyl Sulfone and Diethyl Acetylenedicarboxylate in Comparison to Related Monofunctional Electrophiles
Previously, we determined that diethyl acetylenedicarboxylate (DAD), a protein cross-linker, was significantly more toxic than analogous monofunctional electrophiles. We hypothesized that other protein cross-linkers enhance toxicity similarly. In agreement with this hypothesis, the bifunctional electrophile divinyl sulfone (DVSF) was 6-fold more toxic than ethyl vinyl sulfone (EVSF) in colorectal carcinoma cells and greater than 10-fold more toxic in Saccharomyces cerevisiae. DVSF and DAD caused oligomerization of yeast thioredoxin 2 (Trx2p) in vitro and promoted Trx2p cross-linking to other proteins in yeast at cytotoxic doses. Our results suggest that protein cross-linking is considerably more detrimental to cellular homeostasis than simple alkylation. © 2011 American Chemical Society.
West, James D.; Stamm, Chelsea E.; Brown, Haley A.; Justice, Samantha L.; and Morano, K. A., "Enhanced Toxicity of the Protein Cross-Linkers Divinyl Sulfone and Diethyl Acetylenedicarboxylate in Comparison to Related Monofunctional Electrophiles" (2011). Chemical Research in Toxicology, (9), 1457-1459. 10.1021/tx200302w. Retrieved from https://openworks.wooster.edu/facpub/96