1. Synthesis and pharmacological evaluation of glycine-modified analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE)
Michelle Y H Lai, Margaret A Brimble, David J Callis, Paul W R Harris, Mark S Levi, Frank Sieg Bioorg Med Chem. 2005 Jan 17;13(2):533-48. doi: 10.1016/j.bmc.2004.10.004.
The synthesis of 10 G*PE analogues, wherein the glycine residue has been modified, is described by coupling readily accessible dibenzyl-L-prolyl-L-glutamate 2 with various analogues of glycine. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glycine residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
2. Structural and spectroscopic elucidation of tetrapetide glycyl-(L)-prolyl-glycyl-glycine and its hydrogensquarate
Tsonko M Kolev Protein Pept Lett. 2008;15(7):713-8. doi: 10.2174/092986608785133663.
The IR-spectroscopic and structural elucidation of tetrapeptide glycyl-(L)-prolyl-glycyl-glycine and its hydrogensquarate was performed by employing linear-polarized IR-spectroscopy of oriented colloid suspensions in nematic host as well as mass spectrometry. Quantum-chemical ab initio calculations were carried out in order to evaluate both the electronic structure and optical properties of the compound studied.
3. Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer's Disease
Hasan Turkez, et al. Biomolecules. 2021 Jan 19;11(1):126. doi: 10.3390/biom11010126.
So far, there is no effective disease-modifying therapies for Alzheimer's Disease (AD) in clinical practice. In this context, glycine-L-proline-L-glutamate (GPE) and its analogs may open the way for developing a novel molecule for treating neurodegenerative disorders, including AD. In turn, this study was aimed to investigate the neuroprotective potentials exerted by three novel GPE peptidomimetics (GPE1, GPE2, and GPE3) using an in vitro AD model. Anti-Alzheimer potentials were determined using a wide array of techniques, such as measurements of mitochondrial viability (MTT) and lactate dehydrogenase (LDH) release assays, determination of acetylcholinesterase (AChE), α-secretase and β-secretase activities, comparisons of total antioxidant capacity (TAC) and total oxidative status (TOS) levels, flow cytometric and microscopic detection of apoptotic and necrotic neuronal death, and investigating gene expression responses via PCR arrays involving 64 critical genes related to 10 different pathways. Our analysis showed that GPE peptidomimetics modulate oxidative stress, ACh depletion, α-secretase inactivation, apoptotic, and necrotic cell death. In vitro results suggested that treatments with novel GPE analogs might be promising therapeutic agents for treatment and/or or prevention of AD.
