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

Nicholas S Trotter; Margaret A Brimble; Paul W R Harris; David J Callis; Frank Sieg

doi:10.1016/j.bmc.2004.10.005

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

Bioorg Med Chem. 2005 Jan 17;13(2):501-17. doi: 10.1016/j.bmc.2004.10.005.

Authors

Nicholas S Trotter¹, Margaret A Brimble, Paul W R Harris, David J Callis, Frank Sieg

Affiliation

¹ Neuren Pharmaceuticals Medicinal Chemistry Group, Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland 1000, New Zealand.

PMID: 15598572
DOI: 10.1016/j.bmc.2004.10.005

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Corpus Striatum / cytology
Female
Glutamic Acid / analogs & derivatives*
Glutamic Acid / chemical synthesis
Glutamic Acid / pharmacology
Models, Chemical
Molecular Structure
Neurons / drug effects
Neuroprotective Agents / chemical synthesis*
Neuroprotective Agents / pharmacology*
Okadaic Acid / antagonists & inhibitors
Oligopeptides / chemical synthesis*
Oligopeptides / pharmacology*
Rats
Rats, Wistar

Substances

Neuroprotective Agents
Oligopeptides
Okadaic Acid
Glutamic Acid
glycyl-prolyl-glutamic acid