Disordered proteins, such as those central to Alzheimer's and Parkinson's, are particularly intractable for structure-targeted therapeutic design. Here we demonstrate the capacity of a synthetic foldamer to capture structure in a disease relevant peptide. Oligoquinoline amides have a defined fold with a solvent-excluded core that is independent of its outwardly projected, derivatizable moieties...

Alzheimer’s disease (AD) is a neuroinflammatory based pathologic state in which β-amyloid aggregates are a major devastating agents. In this study, a series of 2-hydroxyiminoethanones were synthesized and evaluated as anti-inflammatory in carrageenan and formalin tests and inhibitors of β-amyloid aggregation. Compounds 1-10b were synthesized through a two-step reaction. Results: Compounds 1-5b ...

We performed ultrastructural testing of a cardiac biopsy taken from a heart with amyloidosis in which transthyretin mutation and light chain A amyloidosis were excluded. Cardiomyocytes of the affected heart showed accumulation of endosomal-like structures in which soluble amyloid oligomeric conformation was deposited. Intracellular accumulation of β -amyloid as well as phosphorylated tau protei...

Amyloidogenesis is associated with more than 30 human diseases, including Alzheimer's which is related to aggregation of β-amyloid peptide (Aβ). Here, consecutive stages of Aβ42 aggregation and amyloid fibril formation were followed electrochemically via oxidation of tyrosines in Aβ42 adsorbed on the basal plane graphite electrode and directly correlated with Aβ42 morphological changes observed...