The two novel diastereoisomeric glutathione analogues 1 and 2 have been designed and synthesized by replacing the native y-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 y-glutamyltranspeptidase (y-GT)and human glutathione S-transferase (hGST P1-1). Both analogues 1 and 2 are completely resistant to enzymatic degradation by y-GT. The S-transferase utilizes the analogue 2 as a good substrate while is unable to bind the analogue 1. 2003 Elsevier Science Ltd. All rights reserved.
Proline-Glutamate Chimeras in Isopeptides., Synthesis and Biological Evaluation of Conformationally Restricted Glutathione Analogues
2003
Abstract
The two novel diastereoisomeric glutathione analogues 1 and 2 have been designed and synthesized by replacing the native y-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 y-glutamyltranspeptidase (y-GT)and human glutathione S-transferase (hGST P1-1). Both analogues 1 and 2 are completely resistant to enzymatic degradation by y-GT. The S-transferase utilizes the analogue 2 as a good substrate while is unable to bind the analogue 1. 2003 Elsevier Science Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.