Amphiphilic oligoamide alpha-helix peptidomimetics inhibit islet amyloid polypeptide aggregation

作者：Kulikov Oleg V; Kumar Sunil; Magzoub Mazin; Knipe Peter C; Saraogi Ishu; Thompson Sam^*; Miranker Andrew D; Hamilton Andrew D

来源：Tetrahedron Letters, 2015, 56(23): 3670-3673.

DOI：10.1016/j.tetlet.2015.02.132

• alpha-Helix mimetics
• Amyloid beta-peptides
• Diabetes
• Helical structures
• Proteomimetics

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 beta-sheet rich aggregates. We have previously reported classes of alpha-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.

• 出版日期2015-6-3