Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. Issue 23 (3rd June 2015)

• Record Type: Journal Article
• Authors: Kulikov, Oleg V.; Kumar, Sunil; Magzoub, Mazin; Knipe, Peter C.; Saraogi, Ishu; Thompson, Sam; Miranker, Andrew D.; Hamilton, Andrew D.
• Is Part Of: Tetrahedron letters. Volume 56:Issue 23(2015)
• Page Start: 3670
• Page End: 3673
• Publication Date: 2015-06-03
• Subjects: α-Helix mimetics -- Amyloid β-peptides -- Diabetes -- Helical structures -- Proteomimetics; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2015.02.132
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: The abnormal deposition of proteins as insoluble plaques is associated with many diseases, including Alzheimer's, Parkinson's and type II diabetes. There is an unmet need for synthetic agents that are able to mediate particular steps in the pathway between soluble proteins in their native unfolded state and their insoluble β-sheet rich aggregates. We have previously reported classes of α-helix mimetic that agonize or antagonize islet amyloid polypeptide aggregation, depending on the presence of a lipid bilayer. Here we investigate a novel mixed benzamide and pyridylamide scaffold that gives improved activity and explores the role of side-chain polarity, backbone rigidity and curvature in inhibiting lipid-catalyzed fibrillization.