Self-assembly of amylin(20-29) amide-bond derivatives into helical ribbons and peptide nanotubes rather than fibrils

Abstract

Uncontrolled aggregation of proteins or polypeptides can be detrimental for normal cellular processes in healthy organisms. Proteins or polypeptides that form these amyloid deposits differ in their primary sequence but share a common structural motif: the (anti)parallel β sheet. A well-accepted approach for interfering with -sheet formation is the design of soluble β-sheet peptides to disrupt the hydrogen-bonding network; this ultimately leads to the disassembly of the aggregates or fibrils. Here, we describe the synthesis, spectroscopic analysis, and aggregation behavior, imaged by electron microscopy, of several backbone-modified amylin(20-29) derivatives. It was found that these amylin derivatives were not able to form fibrils and to some extent were able to inhibit fibril growth of native amylin(20-29). However, two of the amylin peptides were able to form large supramolecular assemblies, like helical ribbons and peptide nanotubes, in which β-sheet formation was clearly absent. This was quite unexpectedWiley-VCH since these peptides have been designed as soluble β-sheet breakers for disrupting the characteristic hydrogen-bonding network of (anti)parallel β sheets. The increased hydrophobicity and the presence of essential amino acid side chains in the newly designed amylin(20-29) derivatives were found to be the driving force for self-assembly into helical ribbons and peptide nanotubes. This example of controlled and desired peptide aggregation may be a strong impetus for research on bionanomaterials in which special shapes and assemblies are the focus of interest. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.