SYNTHESIS OF LABELED CARBOHYDRATES

SIR提供77个Se(94%浓缩)Ebselen；55 mg 94%(77 Se)-二硒(C26H_2N_2，J_2Se_2)；50毫克Ebselen[60940-34-3] 表现出谷胱甘肽过氧化物酶(GPO)样活性，并已被 被认为是一种抗炎药物。它的急性假释。中的毒性 小鼠低剂量(&gt；6000 mg/kg)。然而，有报道称，艾布塞伦 能迅速与能裂解Se-N键的巯基化合物反应。 基于这些发现，人们预计艾布塞伦会对 依赖SH的酶，例如丙酮酸脱氢酶，并将 毒性很大。这一悖论可以通过研究 当分离的细胞暴露在Ebselen中时，Se化合物。我们计划 依布硒(及其衍生物)的共价相互作用研究 含有功能性SH基团的酶和ebselen氧化还原循环 在孤立的细胞中。共价Se相互作用的化学性质是 从相应的~(77)Se核磁共振信号的化学位移中推断出来 使用JEOL SX270型核磁共振波谱仪进行体外实验。高度浓缩 77Se-Ebselen是适当的S/N比率所必需的。校准是 用依贝司林及其二乙醇胺进行治疗。预测试将使用各种 SH功能酶的商品化制剂。全细胞周转 Ebselen与大鼠肝癌细胞(HTC)孵育后的 通过测量特定信号的出现/消失 大约。氯仿提取物中920ppm和450ppm。与之形成鲜明对比的是 用纯化的酶研究依布硒在培养细胞中的去向 很可能受到细胞内谷胱甘肽(GSH)含量的影响。 因此，必须考虑混合硫化物(GSSeR)的形成 在与易思伦周转的中间商打交道时。这些 中间体可能会为观察到的低毒提供解释 埃布塞林在体内的作用。产生GSSG+RSeSeR的GSSeR的错位 为二硒醚在今后的研究中提供了重要的作用。

The SIR provided 77 Se (94% enriched)Ebselen; 55mg 94% (77 Se)-diselenide (C26H2ON2 J2 Se2); 50mg Ebselen [60940-34-3] exhibits glutathioneperoxidase (GPO)-like activity and has been proposed as an anti-inflammatory drug. Its acute p.o. toxicity in mice is low (>6000mg/kg). However, it has been reported that ebselen reacts rapidly with sulfhydryl compounds which cleave the Se-N bond. Based on these findings one would expect ebselen to react with SH-dependent enzymes, e.g., pyruvate dehydrogenase, and to be considerably toxic. This paradoxon might be resolved by examining the Se compounds when isolated cells are exposed to ebselen. We plan to investigate covalent interactions of ebselen (and its derivatives) with enzymes containing functional SH groups and ebselen redox cycling in isolated cells. The chemical nature of covalent Se interactions is deduced from chemical shifts of the corresponding 77Se NMR signals in vitro using a JEOL SX270 NMR spectrometer. Highly enriched 77Se-ebselen is required for appropriate S/N ratios. Calibration is performed with ebselen and its diselenide. Pre-tests will use various commercial preparations of SH-functional enzymes. Whole cell turnover of ebselen after incubation with rat hepatoma cells (HTC) is assessed by measuring the appearance / disappearance of specific signals at approx. 920ppm and 450ppm in chloroform extracts. In contrast to studies with purified enzymes, the fate of ebselen in cultured cells is likely to be affected by cellular glutathione (GSH) contents. Thus, formation of mixed selenosulfides (GSSeR) has to be considered when dealing with intermediates of ebselen turnover. These intermediates may provide an explanation for the observed low toxicity of ebselen in vivo. Dismutation of GSSeR yielding GSSG + RSeSeR provides an important role for the diselenide in future studies