Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity.
Amino Acid Sequence
Amyloid
/ metabolism
Amyloid beta-Peptides
/ chemistry
Cell Death
/ drug effects
Cell Line, Tumor
Galactosamine
/ metabolism
Humans
Inhibitory Concentration 50
Islet Amyloid Polypeptide
/ chemistry
Peptide Fragments
/ chemistry
Protein Aggregates
/ drug effects
Tryptophan
/ metabolism
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
02 09 2020
02 09 2020
Historique:
received:
25
02
2020
accepted:
31
07
2020
entrez:
4
9
2020
pubmed:
4
9
2020
medline:
17
6
2021
Statut:
epublish
Résumé
Self-assembly of proteins into amyloid fibrils is a hallmark of various diseases, including Alzheimer's disease (AD) and Type-2 diabetes Mellitus (T2DM). Aggregation of specific peptides, like Aβ42 in AD and hIAPP in T2DM, causes cellular dysfunction resulting in the respective pathology. While these amyloidogenic proteins lack sequence homology, they all contain aromatic amino acids in their hydrophobic core that play a major role in their self-assembly. Targeting these aromatic residues by small molecules may be an attractive approach for inhibiting amyloid aggregation. Here, various biochemical and biophysical techniques revealed that a panel of tryptophan-galactosylamine conjugates significantly inhibit fibril formation of Aβ42 and hIAPP, and disassemble their pre-formed fibrils in a dose-dependent manner. They are also not toxic to mammalian cells and can reduce the cytotoxicity induced by Aβ42 and hIAPP aggregates. These tryptophan-galactosylamine conjugates can therefore serve as a scaffold for the development of therapeutics towards AD and T2DM.
Identifiants
pubmed: 32879439
doi: 10.1038/s42003-020-01216-5
pii: 10.1038/s42003-020-01216-5
pmc: PMC7468108
doi:
Substances chimiques
Amyloid
0
Amyloid beta-Peptides
0
Islet Amyloid Polypeptide
0
Peptide Fragments
0
Protein Aggregates
0
amyloid beta-protein (1-42)
0
Galactosamine
7535-00-4
Tryptophan
8DUH1N11BX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
484Références
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