Issue 38, 2016

Foldamer scaffolds suggest distinct structures are associated with alternative gains-of-function in a preamyloid toxin

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.

Graphical abstract: Foldamer scaffolds suggest distinct structures are associated with alternative gains-of-function in a preamyloid toxin

  • This article is part of the themed collection: Foldamers

Supplementary files

Article information

Article type
Communication
Submitted
09 2 2016
Accepted
07 4 2016
First published
07 4 2016

Chem. Commun., 2016,52, 6391-6394

Foldamer scaffolds suggest distinct structures are associated with alternative gains-of-function in a preamyloid toxin

S. Kumar, M. Birol and A. D. Miranker, Chem. Commun., 2016, 52, 6391 DOI: 10.1039/C6CC01248E

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