Synthesis and initial characterization of gamma-L-glutamyl-L-thiothreonylglycine and gamma-L-glutamyl-L-allo-thiothreonylglycine as steric probes of the active site of glyoxalase I.
Synthesis and initial characterization of gamma-L-glutamyl-L-thiothreonylglycine and gamma-L-glutamyl-L-allo-thiothreonylglycine as steric probes of the active site of glyoxalase I.
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作为乙二醛酶 I 活性位点空间探针的 γ-L-谷氨酰-L-硫苏氨酰甘氨酸和 γ-L-谷氨酰-L-别基-硫苏氨酰甘氨酸的合成和初步表征。
DOI：
10.1016/0006-291x(91)91975-i
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发表时间：
1991
影响因子：
3.1
通讯作者：
Creighton,DJ
中科院分区：
文献类型：
--
作者：
Xie,XF;Creighton,DJ
合成了非对映体谷胱甘肽衍生物γ-L-Glu-L-allo-thioThr-Gly（6）和γ-L-Glu-L-thioThr-Gly（6a），它们可作为酶结合谷胱甘肽底物半胱氨酰残基附近空间环境的特异性探针。用glycoprotein酶I进行的实验表明，虽然6 α-甲基乙二醛硫代半缩醛是该酶的底物，但6-甲基乙二醛硫代半缩醛与活性位点形成紧密结合的失败复合物（Ki ≤ 100 μM）。显然，谷胱甘肽酶I的正常GSH-甲基乙二醛硫代半缩醛底物的半胱氨酰C β-H s质子的小尺寸是生产性底物结合的严格要求。这些化合物可能为抑制GSH依赖性酶提供新的途径。
The diastereomeric GSH derivatives γ-L-Glu-L-allo-thioThr-Gly (6) and γ-L-Glu-L-thioThr-Gly (6a) have been synthesized as specific probes of the steric environment near the cysteinyl residue of enzyme bound glutathionyl substrates. Experiments with glyoxalase I indicate that while 6a-methylglyoxal thiohemiacetal is a substrate for the enzyme, 6-methylglyoxal thiohemiacetal forms a tight-binding abortive complex with the active site (K i⋍ 100 μM). Apparently, the small size of the cysteinyl C β-H s proton of the normal GSH-methylglyoxal thiohemiacetal substrate for glyoxalase I is a strict requirement for productive substrate binding. These compounds may provide a novel approach to the inhibition of GSH-dependent enzymes.