Synthesis and biological evaluation of the disulfide form of the glutathione analogue gamma-(L-glutamyl)-L-cysteinyl-L-aspartyl-L-cysteine.

By using the chain to chain mode of cyclization the title glutathione analogue (4), containing the 11-membered disulfide ring replacing the native -Cys-Gly fragment, has been synthesized and characterized together with its reduced dithiol form gamma-Glu-Cys-Asp-Cys (5). The activity of (4) with gamma-glutamyl-transferase and glutathione reductase has been evaluated and compared with those of the two conformationally restricted glutathione analogues (2) and (3) previously reported.