Article

Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage.

Dipartimento di Scienze del Farmaco, Università degli Studi G. D'Annunzio, Via dei Vestini, I-66100 Chieti, Italy.
Il Farmaco 10/2003; 58(9):787-93. DOI:10.1016/S0014-827X(03)00135-6 pp.787-93
Source: PubMed

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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Keywords

aspartic acid
 
central cysteine
 
co-substrate
 
H-Glo(-Asp-Gly-OH)-OH
 
H-Glu(-Asp-Gly-OH)-OH
 
hGST P1-1
 
hGSTP1-1
 
human GST P1-1
 
isosteric substitution
 
new GSH analogues 4
 
new GSH analogues H-Glo(-Ser-Gly-OH)-OH
 
O-benzyl derivative 4
 
potent competitive inhibitors
 
rat GST 3-3