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Updated: Mar 22, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Foldamer scaffolds suggest distinct structures are associated with alternative gains-of-function in a preamyloid
Sunil Kumar1, Melissa Birol, Andrew D Miranker
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Andrew.miranker@yale.edu.
Abstract:
An oligoquinoline foldamer library was synthesized and screened for antagonism of lipid bilayer catalysed assembly of islet amyloid polypeptide (IAPP). One tetraquinoline, ADM-116, showed exceptional potency not only in this assay, but also in secondary assays measuring lipid bilayer integrity and rescue of insulin secreting cells from the toxic effects of IAPP. Structure activity studies identified three additional oligoquinolines, closely related to ADM-116, which also have strong activity in the primary, but not the secondary assays. This contrasts work using an oligopyrdyl foldamer scaffold in which all three assays are observed to be correlated. The results suggest that while there is commonality to the structures and pathways of IAPP conformational change, it is nevertheless possible to leverage foldamers to separately affect IAPP's alternative gains-of-function.
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