Synthesis and neuroprotective activity of analogues of glycyl-L-prolyl-L-glutamic acid (GPE) modified at the alpha-carboxylic acid.

The synthesis of nine GPE* analogues, wherein the alpha-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-L-proline 2 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.