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Modulation of Amyloid-?42 Conformation by Small Molecules Through Nonspecific Binding.

ABSTRACT: Aggregation of amyloid-? (A?) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and scyllo-inositol, which are AD drug candidates currently under investigation. We show that both small molecules promote a conformational change of the A?42 monomer toward a more collapsed phase through a nonspecific binding mechanism. This finding provides atomistic-level insights into designing potential drug candidates for future AD treatments.

SUBMITTER: Liang C

PROVIDER: S-EPMC6783347 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Modulation of Amyloid-β42 Conformation by Small Molecules Through Nonspecific Binding.

Liang Chungwen C Savinov Sergey N SN Fejzo Jasna J Eyles Stephen J SJ Chen Jianhan J

Journal of chemical theory and computation 20190904 10

Aggregation of amyloid-β (Aβ) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and <i>scyllo</i>-inositol, which are AD drug candidates currently under investigation. We show that both small molecules promote a conformational change of the Aβ42 monomer toward a more collapsed phase through a non ...[more]

PMID: 31476124

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