Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage.
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.
D000818:Animals; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014520:Urethane / Q000737:chemistry*
D004791:Enzyme Inhibitors; D010455:Peptides; D014520:Urethane; D005982:Glutathione Transferase; D005978:Glutathione