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Updated: Jul 25, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage
I Cacciatore1, A M Caccuri, A Di Stefano
1Dipartimento di Scienze del Farmaco, Università degli Studi G. D'Annunzio, Via dei Vestini, I-66100 Chieti, Italy.
Abstract:
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.
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