Synthesis and pharmacological evaluation of side chain modified glutamic acid analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE).

The synthesis of eight GPE* analogues, wherein the gamma-carboxylic moiety of the glutamic residue has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-L-proline with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.