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

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Item Type:	Article
Title:	Foldamer scaffolds suggest distinct structures are associated with alternative gains-of-function in a preamyloid toxin
Creators Name:	Kumar, S., Birol, M. and Miranker, A.D.
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.
Keywords:	Amyloid beta-Peptides, Insulin-Secreting Cells, Lipid Bilayers, Molecular Structure, Quinolines
Source:	Chemical Communications
ISSN:	1359-7345
Publisher:	Royal Society of Chemistry
Volume:	52
Number:	38
Page Range:	6391-6394
Date:	11 May 2016
Official Publication:	https://doi.org/10.1039/c6cc01248e
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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