Modulation of fibrillation of hIAPP core fragments by chemical modification of the peptide backbone

► We examine backbone contribution to fibril stability using modified peptides. ► The backbone is extremely sensitive to substitutions. ► One analogue could elongate fibril seeds, none could fibrillate on their own. ► The resulting fibrils display differences in secondary structure and morphology. ► Side-chain mutations had little effect on fibrillation kinetics and stability.