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Rational Design of a Cocktail of Inhibitors against Aβ Aggregation
Author(s) -
Li Gao,
Yang WuYue,
Li WenHao,
Luo YunYi,
Lim YehJun,
Li Yang,
Paul Ashim,
Segal Daniel,
Hong Liu,
Li YanMei
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905621
Subject(s) - chemistry , nucleation , monomer , fibril , rational design , biophysics , kinetics , small molecule , molecule , amyloid (mycology) , elongation , amyloid fibril , protein aggregation , combinatorial chemistry , biochemistry , amyloid β , polymer , nanotechnology , biology , materials science , organic chemistry , medicine , inorganic chemistry , physics , disease , pathology , quantum mechanics , ultimate tensile strength , metallurgy
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.