Sensor mechanism of lipophilic ligands

食品中的亲电性物质与人类健康和疾病有关。它们与蛋白质反应，产生特殊的加合物结构，可以作为配体发挥作用。异硫氰酸酯是一种与硫醇形成加合物的透膜亲电剂，已被认为具有重要的医疗保健作用。为了深入了解异硫氰酸酯诱导的细胞反应，我们设计了一种新的探针，结合了异硫氰酸酯反应基团和炔的官能团，揭示了当暴露于6-HITC时，细胞内蛋白质的硫代氨基甲酰化。硫代氨基甲酰化的靶点包括热休克蛋白90b(Hsp90b)，它是Hsp90家族中的一个伴侣ATPase，与蛋白质成熟和靶向有关。对Hsp90b硫代氨基甲酰化的进一步研究表明，6-HITC-Hsp90b偶联物的形成可能导致热休克因子-1的激活，从而迅速发出潜在的热休克反应信号。

Electrophiles in food have been implicated in human health and disease. They react with proteins and generate specific adduct structures that could function as ligands. Isothiocyanates, membrane-permeable electrophiles that form adducts with thiols, have been suggested to have important medical benefits. To gain a chemical insight into the cellular response induced by isothiocyanates, we designed a novel probe, combining an isothiocyanate-reactive group and an alkyne functionality, and revealed that the thiocarbamoylation of proteins occurred in the cells upon exposure to 6-HITC. The target of thiocarbamoylation included heat shock protein 90b (Hsp90b), a chaperone ATPase of the Hsp90 family implicated in protein maturation and targeting. Further study on the thiocarbamoylation of Hsp90b suggested that the formation of 6-HITC-Hsp90b conjugate might cause activation of heat shock factor-1, rapidly signaling a potential heat shock response.