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Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease
Author(s) -
Acharya Srabasti,
Srivastava Kinshuk R.,
Nagarajan Sureshbabu,
Lapidus Lisa J.
Publication year - 2016
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201600706
Subject(s) - chemistry , intramolecular force , peptide , monomer , quenching (fluorescence) , control reconfiguration , biophysics , protein aggregation , diffusion , kinetic energy , fluorescence , stereochemistry , biochemistry , organic chemistry , polymer , thermodynamics , physics , quantum mechanics , computer science , biology , embedded system
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 Aβ 40 , which aggregates slowly, than that for Aβ 42 , which aggregates quickly. Furthermore, the rate of reconfiguration for Aβ 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 Aβ peptide and provide a kinetic basis for why Aβ 42 is more prone to aggregation than Aβ 40 , despite a difference of only two amino acids.