Enhanced toxicity of the protein cross-linkers divinyl sulfone and diethyl acetylenedicarboxylate in comparison to related monofunctional electrophiles.
Enhanced toxicity of the protein cross-linkers divinyl sulfone and diethyl acetylenedicarboxylate in comparison to related monofunctional electrophiles.
复制标题
与相关的单功能亲电子试剂相比，蛋白质交联剂二乙烯基砜和乙炔二甲酸二乙酯的毒性增强。
DOI：
10.1021/tx200302w
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发表时间：
2011
影响因子：
4.1
通讯作者：
Morano,KevinA
中科院分区：
文献类型：
--
作者：
West,JamesD;Stamm,ChelseaE;Brown,HaleyA;Justice,SamanthaL;Morano,KevinA
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 inSaccharomyces cerevisiae. DVSF and DAD caused oligomerization of yeast thioredoxin 2 (Trx2p)in vitroand 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.
