Rational Design of a Cocktail of Inhibitors against Aβ Aggregation

It has been reported that many molecules could inhibit the aggregation of Aβ (amyloid‐β) through suppressing either primary nucleation, secondary nucleation, or elongation processes. In order to suppress multiple pathways of Aβ aggregation, we screened 23 small molecules and found two types of inhib...

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Bibliographic Details
Published in:Chemistry : a European journal 2020-03, Vol.26 (16), p.3499-3503
Main Authors: Li, Gao, Yang, Wu‐Yue, Li, Wen‐Hao, Luo, Yun‐Yi, Lim, Yeh‐Jun, Li, Yang, Paul, Ashim, Segal, Daniel, Hong, Liu, Li, Yan‐Mei
Format: Article
Language:English
Subjects:
Agglomeration
Amyloid
amyloid beta-peptides
Amyloid beta-Peptides - antagonists & inhibitors
Amyloid beta-Peptides - chemistry
Biological Products - chemistry
Biological Products - pharmacology
Chemical kinetics
chemical kinetics analysis
Chemistry
cocktail
Drug Design
Elongation
inhibitor
Inhibitors
Kinetics
Monomers
Natural products
Nucleation
Reaction kinetics
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Summary:It has been reported that many molecules could inhibit the aggregation of Aβ (amyloid‐β) through suppressing either primary nucleation, secondary nucleation, or elongation processes. In order to suppress multiple pathways of Aβ aggregation, we screened 23 small molecules and found two types of inhibitors with different inhibiting mechanisms based on chemical kinetics analysis. Trp‐glucose conjugates (AS2) could bind with fibril ends while natural products (D3 and D4) could associate with monomers. A cocktail of these two kinds of molecules achieved co‐inhibition of various fibrillar species and avoid unwanted interference. A cocktail of several inhibitors which could bind with different species of Aβ aggregates simultaneously and achieve co‐inhibition of Aβ fibrillation, without any unwanted interference observed.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201905621