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Effect of Chirality and Chimeras on Amyloid Aggregation

  • Author(s): Le, Kim Virginia
  • Advisor(s): Nowick, James S
  • et al.
Abstract

This thesis reports the activity of macrocyclic β-sheets and their activity against amyloid aggregation. Macrocyclic D-amino acid β-sheets delay or suppress amyloid aggregation at substoichiometric concentrations and show increased activity compared to their L-enantiomers. Fluorescence assays highlight differences between enantiomers and transmission electron microscopy shows the absence of amyloid fibrils in the presence of D-amino acid macrocycles. The diastereomers of the D-amino acid macrocycles are less effective in halting amyloid aggregation. Macrocyclic β-sheet chimeras can suppress or delay amyloid aggregation at stoichiometric amounts. Fluorescence assays show macrocycles containing Aβ-tau hybrid sequences interact with amyloids and delay fibrillization. These studies indicate amyloidogenic peptides are sensitive to chirality and can participate in interactions with chimera peptides.

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