Analogues of the neuroprotective tripeptide Gly-Pro-Glu (GPE): synthesis and structure–activity relationships

A series of GPE analogues, including modifications at the Pro and/or Glu residues, was prepared and evaluated for their NMDA binding and neuroprotective effects. Main results suggest that the pyrrolidine ring puckering of the Pro residue plays a key role in the biological responses, while the preference for cis or trans rotamers around the Gly-Pro peptide bond is not important.This work has been supported by the Spanish Ministry of Education and Science (SAF2003-07207-C02). S.A.A.D.D. holds a predoctoral fellowship from this Ministry for Associated Units to CSIC.Peer reviewe