SYNTHESIS OF LABELED CARBOHYDRATES

SIR提供77硒（94%富集）依布硒仑; 55 mg 94%（77 Se）-二硒醚（C26 H2ON 2 J2 Se 2）; 50 mg依布硒啉[60940-34-3] 表现出谷胱甘肽过氧化物酶（GST）样活性， 被推荐为抗炎药。 它的急性穿孔。毒性 小鼠低（> 6000 mg/kg）。 然而，据报道， 与巯基化合物迅速反应，使Se-N键断裂。 基于这些发现，人们会期望埃布硒啉与 SH依赖性酶，例如，丙酮酸脱氢酶， 相当有毒。 这个悖论可以通过检查 当分离的细胞暴露于依布硒啉时，硒化合物。 我们计划 研究依布硒啉（及其衍生物）共价相互作用 用含有功能性SH基团和依布硒啉氧化还原循环的酶 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 NMR信号的化学位移推断， 使用JEOL SX 270 NMR光谱仪在体外测定。 高浓缩 适当的S/N比需要77 Se-ebselen。 校准 用依布硒啉及其二硒化物进行。 预测试将使用各种 SH功能酶的商业制剂。 全细胞更新 评估与大鼠肝癌细胞（HTC）孵育后依布硒啉的浓度 通过测量特定信号的出现/消失， 约 920 ppm和450 ppm。 相比 用纯化的酶研究了依布硒啉在培养细胞中的命运 可能受细胞谷胱甘肽（GSH）含量的影响。 因此，必须考虑混合硒硫化物（GSSeR）的形成 当处理依布硒啉周转的中间体时。 这些 中间体可以解释观察到的低毒性 体内的依布硒啉。 GSSeR歧化产生GSSG + RSeSeR 为二硒醚在未来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