Chen W J, Boehlert C C, Rider K, Armstrong R N
Biochem Biophys Res Commun. 1985 Apr 16;128(1):233-40. doi: 10.1016/0006-291x(85)91669-9.
The oxygen analogue, gamma-L-Glu-L-SerGly (GOH) and desthio analogue, gamma-L-Glu-L-AlaGly (GH) have been synthesized by a simple three step procedure involving active ester coupling of N-t-BOC-alpha-(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 KI values of 13.0 and 116 microM, 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.
通过一个简单的三步程序合成了氧类似物γ-L-谷氨酰-L-丝氨酰甘氨酸（GOH）和脱硫类似物γ-L-谷氨酰-L-丙氨酰甘氨酸（GH），该程序分别涉及N-叔丁氧羰基-α-（4-硝基苯基）-L-谷氨酸与L-丝氨酰甘氨酸和L-丙氨酰甘氨酸的活性酯偶联。这两种肽是大鼠肝脏谷胱甘肽S-转移酶同工酶3-3和4-4的优秀终止抑制剂。在1-氯-2,4-二硝基苯（CDNB）的低固定浓度下，GOH和GH是同工酶3-3对谷胱甘肽的线性竞争性抑制剂，其抑制常数（KI）值分别为13.0和116微摩尔。当谷胱甘肽为固定底物时，这两种肽对CDNB均为非竞争性（混合型）抑制剂。两种肽与同工酶4-4也得到了类似的结果。这些结果排除了亲电试剂先加成的有序或乒乓动力学机制。
