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Issue 37, 2018
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A solution NMR toolset to probe the molecular mechanisms of amyloid inhibitors

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Abstract

The self-association of the amyloid beta (Aβ) peptide into toxic oligomers is implicated in the early events leading to Alzheimer's disease (AD). Blocking the formation of Aβ oligomers and their interactions with the extracellular and cellular environment through small molecules and biopharmaceuticals is therefore a promising preventive strategy for AD. However, given the heterogeneity and transient nature of the Aβ oligomeric species, detailed structural and kinetic characterizations of such oligomers and oligomer:inhibitor complexes have proven to be challenging. Here, we discuss recent advancements in solution NMR that have been instrumental in overcoming these limitations and we provide two representative examples of Aβ inhibitors from our work to demonstrate the applications of such experiments, i.e. EGCG and human serum albumin.

Graphical abstract: A solution NMR toolset to probe the molecular mechanisms of amyloid inhibitors

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Publication details

The article was received on 17 Feb 2018, accepted on 05 Apr 2018 and first published on 16 Apr 2018


Article type: Feature Article
DOI: 10.1039/C8CC01380B
Citation: Chem. Commun., 2018,54, 4644-4652
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    A solution NMR toolset to probe the molecular mechanisms of amyloid inhibitors

    R. Ahmed and G. Melacini, Chem. Commun., 2018, 54, 4644
    DOI: 10.1039/C8CC01380B

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