The two novel diastereoisomeric glutathione analogues 1 and 2 have been designed and synthesized by replacing the native gamma-glutamylic moiety with the conformational rigid skeleton of cis- or trans-4-carboxy-L-proline residue. Both analogues have been obtained by following the solution phase peptide chemistry methodologies and final reduction of the corresponding disulfide forms 13 and 14. The two analogues 1 and 2 have been tested towards gamma-glutamyltranspeptidase (gamma-GT) and human glutathione S-transferase (hGST P1-1). Both analogues 1 and 2 are completely resistant to enzymatic degradation by gamma-GT. The S-transferase utilizes the analogue 2 as a good substrate while is unable to bind the analogue 1.
Paradisi, M., Mollica, A., Cacciatore, I., Di Stefano, A., Pinnen, F., Caccuri, A.m., et al. (2003). Proline-glutamate chimeras in isopeptides. Synthesis and biological evaluation of conformationally restricted glutathione analogues. BIOORGANIC & MEDICINAL CHEMISTRY, 11(8), 1677-1683 [10.1016/S0968-0896(03)00041-5].
Proline-glutamate chimeras in isopeptides. Synthesis and biological evaluation of conformationally restricted glutathione analogues
CACCURI, ANNA MARIA;RICCI, GIORGIO;
2003-04-17
Abstract
The two novel diastereoisomeric glutathione analogues 1 and 2 have been designed and synthesized by replacing the native gamma-glutamylic moiety with the conformational rigid skeleton of cis- or trans-4-carboxy-L-proline residue. Both analogues have been obtained by following the solution phase peptide chemistry methodologies and final reduction of the corresponding disulfide forms 13 and 14. The two analogues 1 and 2 have been tested towards gamma-glutamyltranspeptidase (gamma-GT) and human glutathione S-transferase (hGST P1-1). Both analogues 1 and 2 are completely resistant to enzymatic degradation by gamma-GT. The S-transferase utilizes the analogue 2 as a good substrate while is unable to bind the analogue 1.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
