Synthesis, biological evaluation and metadynamics simulations of novel <i>N</i>-methyl β-sheet breaker peptides as inhibitors of Alzheimer's β-amyloid fibrillogenesis
Federica Moraca, Ilaria Vespoli, Domenico Mastroianni, Vincenzo Piscopo, Rosa Gaglione, Angela Arciello, Mauro De Nisco, Severina Pacifico, Bruno Catalanotti, Silvana Pedatella
Abstract
-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 2 and 3 prepared and analyzed for their fibrillogenesis inhibition activity and cytotoxicity. An HR-MS-based cell metabolomic approach highlighted their cell permeability properties.
Topics & Concepts
FibrillogenesisPharmacophoreMetadynamicsChemistryBeta sheetIn vitroCombinatorial chemistryPeptideStereochemistryBiochemistryMolecular dynamicsComputational chemistryComputational Drug Discovery MethodsAlzheimer's disease research and treatmentsChemical Synthesis and Analysis