BibTeX
CSL-JSON
MLA
Harvard
Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability ACS Paragon Plus Environment Journal of Medicinal Chemistry Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability
release_akaq34mb5rhrvi5gyn2npep654
by
Julia Kaffy,
Dimitri Brinet,
Jean-Louis Soulier,
Isabelle Correia,
Nicolo Tonali,
Katia Fera,
Yasmine Iacone,
Anaïs Hoffmann,
Lucie Khemtémourian,
Benoit Crousse,
Mark Taylor,
David Allsop
(+3 others)
Released
as a article-journal
.
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 Aβ 1-42 early oligomerization and fibrillization. A wide range of bio-and physico-chemical 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 Aβ 1-42. We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of non-toxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of Aβ 1-42 towards SH-SY5Y neuroblastoma cells, even at sub-stoichiometric 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 Aβ 1-42 aggregation.
In text/plain format
Archived Files and Locations
application/pdf
1.1 MB
file_mfmiiu2ljbao7buklugxkhbqqy
|
web.archive.org (webarchive) eprints.lancs.ac.uk (web) |
Read Archived PDF
Preserved and Accessible
Type
Stage
article-journalStage
unknown
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
access all versions, variants, and formats of this works (eg, pre-prints)
Cite This
Lookup Links