Synthesis and biological evaluation of novel analogues of Gly-l-Pro-l-Glu (GPE) as neuroprotective agents |
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Authors: | Lisa Marinelli Erika Fornasari Antonio Di Stefano Hasan Turkez Salvatore Genovese Francesco Epifano Giuseppe Di Biase Erica Costantini Chiara DAngelo Marcella Reale Ivana Cacciatore |
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Institution: | 1. Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Italy;2. Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey;3. Department of Medical, Oral and Biotechnological Science, University “G. d’Annunzio” of Chieti-Pescara, Italy |
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Abstract: | This study investigated the anti-inflammatory effects of novel pseudotripeptides (GPE 1–3) as potential candidates to counteract neuroinflammation processes in Alzheimer’s disease.GPE 1–3 pseudotripeptides are synthetic derivatives of Gly-l-Pro-l-Glu (GPE), the N-terminal tripeptide of IGF-1, obtained through the introduction of isosteres of the amidic bond (aminomethylene unit) to increase the metabolic stability of the native tripeptide. The results showed that all synthetic derivatives possessed higher half-lives (t1/2?>?4?h) than GPE (t1/2?=?30?min) in human plasma and had good water solubility. The biological results demonstrated that GPE 1–3 had protective properties in several experimental models of treated THP-1 cells. Notably, the novel pseudotripeptides influenced inflammatory cytokine expression (IL-1β, IL-18, and TNF-α) in Aβ25–35-, PMA-, and LPS-treated THP-1 cells. In PMA-differentiated THP-1 macrophages, both GPE 1 and GPE 3 reduced the expression levels of all selected cyto-chemokines, even though GPE 3 showed the best neuroprotective properties. |
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Keywords: | Alzheimer’s disease Neuroinflammation Pseudopeptides |
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