Synthesis and characterization of the oxygen and desthio analogues of glutathione as dead-end inhibitors of glutathione S-transferase.
Synthesis and characterization of the oxygen and desthio analogues of glutathione as dead-end inhibitors of glutathione S-transferase.
复制标题
作为谷胱甘肽 S-转移酶的死端抑制剂的谷胱甘肽氧和脱硫类似物的合成和表征。
DOI：
10.1016/0006-291x(85)91669-9
复制
发表时间：
1985
影响因子：
3.1
通讯作者：
Armstrong,RN
中科院分区：
文献类型：
--
作者：
Chen,WJ;Boehlert,CC;Rider,K;Armstrong,RN
以Nt-BOC-α-（4-硝基苯基）-L-谷氨酸为起始原料，经活性酯偶联三步反应分别合成了含氧类似物γ-L-Glu-L-SerGly（GOH）1和脱硫类似物γ-L-Glu-L-AlaGly（GH）。这两种肽是大鼠肝谷胱甘肽S-转移酶同工酶3-3和4-4的优良死端抑制剂。在低浓度下，GOH和GH对同工酶3-3和谷胱甘肽具有线性竞争性抑制作用，KI值分别为13.0和116 μM。当谷胱甘肽是固定底物时，这两种肽与CDNB相比是非竞争性（混合型）抑制剂。用肽和同工酶4-4获得了类似的结果。结果排除了有序或乒乓动力学机制，其中亲电体添加第一。
The oxygen analogue, γ-L-Glu-L-SerGly (GOH) 1 and desthio analogue, γ-L-Glu-L-AlaGly (GH) have been synthesized by a simple three step procedure involving active ester coupling of Nt-BOC-α-(4-nitrophenyl)-L-glutamate to L-SerGly and L-AlaGly, respectively. The two peptides are excellent dead-end inhibitors of isozymes 3-3 and 4-4 of rat liver glutathione S-transferase. At low fixed concentrations of 1-chloro-2, 4-dinitrobenzene (CDNB) GOH and GH are linear competitive inhibitors of isozyme 3-3 vs glutathione with K I values of 13.0 and 116 μM, respectively. Both peptides are non-competitive (mixed-type) inhibitors vs CDNB when glutathione is the fixed substrate. Similar results are obtained with both peptides and isozyme 4-4. The results rule out ordered or ping-pong kinetic mechanisms where the electrophile adds first.