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.