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Scaffolded multimers of hIAPP20–29 peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP20–29 peptide fragment Proteins and proteomics

Christoffersen, Heidi F., Andreasen, Maria, Zhang, Shuai, Nielsen, Erik Holm, Christiansen, Gunna, Dong, Mingdong, Skrydstrup, Troels, Otzen, Daniel E.
Biochimica et biophysica acta 2015 v.1854 no.12 pp. 1890-1897
Fourier transform infrared spectroscopy, amyloid, atomic force microscopy, cyclodextrins, fluorescence, humans, image analysis, nanomaterials, polypeptides, transmission electron microscopy
Applying fibril-forming peptides in nanomaterial design is still challenged by the difficulties in understanding and controlling how fibrils form. The present work investigates the influence of motional restriction on peptide fibrillation. We use cyclotriphosphazene and cyclodextrin as templates to make conjugates of the fibril-forming core of human islet amyloid polypeptide. Attachment of the peptide to the templates resulted in multimers containing six peptide fragments at different positions. ThT fluorescence, CD and FTIR spectroscopy, and AFM and TEM imaging reveal that in both conjugates the peptide retained its fibrillating properties and formed fibrils. However, the conjugate fibrils formed more rapidly than the free peptide and were long and thin, as opposed to the thick and twisted morphology of the intact peptide. Thus the motional restrictions introduced by the scaffold modulate the structure of the fibrils but do not impede the actual fibrillation process.