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

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

doi:10.1016/j.bmc.2004.10.006

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

Bioorg Med Chem. 2005 Jan 17;13(2):519-32. doi: 10.1016/j.bmc.2004.10.006.

Authors

Margaret A Brimble¹, Nicholas S Trotter, Paul W R Harris, Frank Sieg

Affiliation

¹ Neuren Pharmaceuticals, Medicinal Chemistry Group, Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland 1000, New Zealand. m.brimble@auckland.ac.nz

PMID: 15598573
DOI: 10.1016/j.bmc.2004.10.006

Abstract

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.

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