SELECTIVE-INHIBITION OF GAMMA-GLUTAMYL-CYCLE ENZYMES BY SUBSTRATE ANALOGS
SELECTIVE-INHIBITION OF GAMMA-GLUTAMYL-CYCLE ENZYMES BY SUBSTRATE ANALOGS
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DOI：
10.1073/pnas.74.8.3330
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发表时间：
1977-01-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
GRIFFITH, OW;MEISTER, A
获得了选择性抑制γ-半胱氨酸的反应的底物类似物。谷氨酰循环或仅对有限的代谢周期敏感。因此，谷胱甘肽的合成可以被抑制，并且可以合成不参与转肽作用的谷胱甘肽类似物。羊脑γ-的特异性抑制剂获得谷氨酰环转移酶和大鼠肾5-氧代脯氨酸酶。这些发现提供了新的方法，在体内研究的周期，也更具体地指导类似物的抑制剂，如蛋氨酸亚砜亚胺和6-重氮-5-氧正亮氨酸的设计。
Substrate analogs were obtained that selectively inhibit the reactions of the .gamma.-glutamyl cycle or that were susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis could be inhibited and analogs of glutathione could be synthesized that do not participate in transpeptidation. Specific inhibitors of sheep brain .gamma.-glutamylcyclotransferase and rat kidney 5-oxoprolinase were obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine.