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Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease.

ABSTRACT: The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (A?) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for A?40 , which aggregates slowly, than that for A?42 , which aggregates quickly. Furthermore, the rate of reconfiguration for A?42 speeds up at higher pH, which slows aggregation, and in the presence of the aggregation inhibitor curcumin. The measured reconfiguration rates are able to predict the early aggregation behavior of the A? peptide and provide a kinetic basis for why A?42 is more prone to aggregation than A?40 , despite a difference of only two amino acids.

SUBMITTER: Acharya S

PROVIDER: S-EPMC5806154 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease.

Acharya Srabasti S Srivastava Kinshuk R KR Nagarajan Sureshbabu S Lapidus Lisa J LJ

Chemphyschem : a European journal of chemical physics and physical chemistry 20160915 21

The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (Aβ) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for Aβ40 , which aggregates slowly, than that for Aβ42 , which aggregates quickly. Furthermore, the ...[more]

PMID: 27490673

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