Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors.

ABSTRACT: Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitativ

SUBMITTER: Michaels TCT 

PROVIDER: S-EPMC7533883 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature