Selectively N‐Methylated Soluble IAPP Mimics as Potent IAPP Receptor Agonists and Nanomolar Inhibitors of Cytotoxic Self‐Assembly of Both IAPP and Aβ40

Abstract

The selective incorporation of N-methyl groups in the highly amyloidogenic and cytotoxic sequence of the type 2 diabetes islet amyloid polypeptide (IAPP) generates a unique class of soluble and nontoxic IAPP mimics. These polypeptides combine potent IAPP receptor agonism with nanomolar-affinity inhibitory potential on the amyloid formation and cell-damaging effects of both IAPP and the Alzheimer's β-amyloid peptide (Aβ40).