Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease
Gabriella T. Heller, Francesco A. Aprile, Thomas C. T. Michaels, Ryan Limbocker, Michele Perni, Francesco Simone Ruggeri, Benedetta Mannini, Thomas Löhr, Massimiliano Bonomi, Carlo Camilloni, Alfonso De Simone, Isabella C. Felli, Roberta Pierattelli, Tuomas P. J. Knowles, Christopher M. Dobson, Michele Vendruscolo
Abstract
model of Aβ-associated toxicity, consistent with the mechanism of action identified from the in silico and in vitro studies. These results illustrate the strategy of stabilizing the monomeric states of disordered proteins with small molecules to alter their behavior for therapeutic purposes.
Topics & Concepts
Small moleculeIn silicoDrug discoveryChemistryMonomerBiophysicsAmyloid (mycology)DrugProtein–protein interactionCaenorhabditis elegansPeptideIntrinsically disordered proteinsComputational biologyBiochemistryBiologyPharmacologyInorganic chemistryGeneOrganic chemistryPolymerAlzheimer's disease research and treatmentsProtein Structure and DynamicsComputational Drug Discovery Methods