Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability - Sorbonne Université Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2016

Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability

Abstract

How anti-Alzheimer’s drug candidates that reduce amyloid 1–42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein the capacity of sugar-based peptidomimetics to inhibit both Aβ1–42 early oligomerization and fibrillization. A wide range of bio- and physicochemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, and surface plasmon resonance, were used to identify how these new molecules can delay the aggregation of Aβ1–42. We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of nontoxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of Aβ1–42 toward SH-SY5Y neuroblastoma cells, even at substoichiometric concentrations. Furthermore, demonstration that the best molecule combines hydrophobic moieties, hydrogen bond donors and acceptors, ammonium groups, and a hydrophilic β-sheet breaker element provides valuable insight for the future structure-based design of inhibitors of Aβ1–42 aggregation.
Fichier principal
Vignette du fichier
JmedChemRevised_submitted.pdf (1.07 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-02467871 , version 1 (04-03-2024)

Identifiers

Cite

Julia Kaffy, Dimitri Brinet, Jean-Louis Soulier, Isabelle Correia, Nicolo Tonali, et al.. Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability. Journal of Medicinal Chemistry, 2016, 59 (5), pp.2025-2040. ⟨10.1021/acs.jmedchem.5b01629⟩. ⟨hal-02467871⟩
180 View
1 Download

Altmetric

Share

Gmail Facebook X LinkedIn More