Amyloidogenesis of the amylin analogue pramlintide.

Pramlintide, a triple proline amylinomimetic, was shown to assemble into multimers and form amyloid fibrils in vitro in a pH-dependent manner within hours, as demonstrated by ion mobility spectrometry, thioflavin T fluorescence, electron microscopy, atomic force microscopy, and X-ray diffraction.

The study used ion mobility spectrometry-based mass spectrometry to detect pramlintide multimers and monitored amyloid fibril formation in vitro using thioflavin T fluorescence assays, peptide solubility quantification, transmission electron microscopy, atomic force microscopy, and X-ray diffraction.

Understanding pramlintide's ability to form amyloid fibers is crucial for peptide drug development and safety, as amyloid formation can impact drug stability and potential side effects in diabetic treatments.

The study was conducted in vitro and may not fully represent amyloid formation behavior in living organisms; the clinical implications of pramlintide amyloidogenesis remain unclear.