| Autor: |
Moraca, Federica, Vespoli, Ilaria, Mastroianni, Domenico, Piscopo, Vincenzo, Gaglione, Rosa, Arciello, Angela, De Nisco, Mauro, Pacifico, Severina, Catalanotti, Bruno, Pedatella, Silvana |
| Zdroj: |
MedChemComm; 2024, Vol. 15 Issue: 7 p2286-2299, 14p |
| Abstrakt: |
Several scientific evidences report that a central role in the pathogenesis of Alzheimer's disease is played by the deposition of insoluble aggregates of β-amyloid proteins in the brain. Because Aβ is self-assembling, one possible design strategy is to inhibit the aggregation of Aβ peptides using short peptide fragments homologous to the full-length wild-type Aβ protein. In the past years, several studies have reported on the synthesis of some short synthetic peptides called β-sheet breaker peptides (BSBPs). Herein, we present the synthesis of novel (cell-permeable) N-methyl BSBPs, designed based on literature information on the structural key features of BSBPs. Three-dimensional GRID-based pharmacophore peptide screening combined with PT-WTE metadynamics was performed to support the results of the design and microwave-assisted synthesis of peptides 2and 3prepared and analyzed for their fibrillogenesis inhibition activity and cytotoxicity. An HR-MS-based cell metabolomic approach highlighted their cell permeability properties. |
| Databáze: |
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