Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage.
Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage.
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DOI：
10.1016/s0014-827x(03)00135-6
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Sozio, P.
中科院分区：
文献类型：
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作者：
Cacciatore, I.;Caccuri, A. M.;Sozio, P.
合成并表征了新的谷胱甘肽类似物H-Glo(-Ser-Gly-OH)-OH(5)及其o -苄基衍生物4和H-Glo(-Asp-Gly-OH)-OH(9)，其特征是用丝氨酸或天冬氨酸取代中心半胱氨酸，并含有脲酸片段作为可剪切的γ -谷氨酸连接的等构取代。与H-Glu(-Ser-Gly-OH)-OH和H-Glu(-Asp-Gly-OH)-OH相比，它们抑制人GST P1-1 （hGST P1-1）的能力已被评估，H-Glu(-Ser-Gly-OH)-OH是大鼠GST 3-3和4-4的有效竞争性抑制剂。为了进一步研究等构取代对新的谷胱甘肽类似物4、5和9结合能力的影响，先前报道的含半胱氨酸类似物H-Glo(-Cys-Gly-OH)-OH也被评估为hGSTP1-1的共底物。
The new GSH analogues H-Glo(-Ser-Gly-OH)-OH (5), its O-benzyl derivative 4, and H-Glo(-Asp-Gly-OH)-OH (9), characterized by the replacement of central cysteine with either serine or aspartic acid, and containing an urethanic fragment as isosteric substitution of the scissile gamma-glutamylic junction, have been synthesized and characterized. Their ability to inhibit human GST P1-1 (hGST P1-1) in comparison with H-Glu(-Ser-Gly-OH)-OH and H-Glu(-Asp-Gly-OH)-OH, which are potent competitive inhibitors of rat GST 3-3 and 4-4, has been evaluated. In order to further investigate the effect of the isosteric substitution on the binding abilities of the new GSH analogues 4, 5 and 9, the previously reported cysteinyl-containing analogue H-Glo(-Cys-Gly-OH)-OH has been also evaluated as a co-substrate for hGSTP1-1.