Title
Amyloidogenesis of the amylin analogue pramlintide
Author
Dayana Cabral da Silva, Giselle N. Fontes, Luiza C.S. Erthal, Luís Maurício T.R. Lima
Year
2016
Journal
Biophysical Chemistry
Abstract
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.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Aggregation, Chemical stability, Biochemistry