Transformation of the amyloidogenic peptide amylin(20–29) into its corresponding peptoid and retropeptoid: Access to both an amyloid inhibitor and template for self-assembled supramolecular tapes

The highly amyloidogenic peptide sequence of amylin(20–29) was transformed into its corresponding peptoid and retropeptoid sequences to design a novel class of β-sheet breaker peptides as amyloid inhibitors. This report describes the synthesis of the chiral peptoid building block of l-isoleucine, the solid phase synthesis of the peptoid and retropeptoid sequences of amylin(20–29), and the structural analysis of these amylin derivatives in solution by infrared spectroscopy, circular dichroism, and transmission electron microscopy. It was found that the peptoid sequence did not form amyloid fibrils or any other secondary structures and was able to inhibit amyloid formation of native amylin(20–29). Although the retropeptoid did not form amyloid fibrils it had only modest amyloid inhibitor properties since supramolecular tapes were formed.

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