Amyloidogenesis of the amylin analogue pramlintide

•Pramlintide (25,28,29 Pro-human amylin) is an amylinomimetic compound.•Pramlintide assembly into oligomers as observed by ESI-IMS-MS•Pramlintide was shown to aggregate at mild acidic to neutral solutions.•The amyloid nature of pramlintide aggregates were confirmed by TEM, AFM, XRD, FTIR.•The results suggest an universal amyloid behavior of amylin analogues.

Amylin is a pancreatic peptide hormone co-secreted along with insulin by the β-cells. It is found in amyloid deposits in both type 2 diabetic individuals and elder non-diabetic. The triple proline amylinomimetic compound (25,28,29-Pro-human amylin) named pramlintide was designed aiming to solve the solubility and amyloid characteristics of human amylin. We have found by using ion mobility spectrometry-based mass spectrometry that pramlintide is able to assembly into multimers. Pramlintide formed amyloid fibrils in vitro in a pH-dependent kinetic process within a few hours, as followed by thioflavin T, quantification of soluble peptide and further characterized by transmission electron microscopy, atomic force microscopy and X-ray diffraction. These data indicate that pramlintide can form amyloid fibers.

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