EXPLORING THE INHIBITION MECHANISMS OF AMYLOID PROTOFIBRILS USING FOURIER TRANSFORM ION CYCLOTRON RESONANCE-MASS SPECTROMETRY (FTICR-MS)

摘要

Human Islet Amyloid Polypeptide (hIAPP) is an amyloidogenic protein that aggregates rapidly in humans. Classic structure-based design for therapeutics cannot apply to amyloid protein drug development as most amyloid proteins are inherently disordered. Herein, Fourier Transform Ion Cyclotron Resonance (FTICR) MS was used to study the potential inhibitors, identify binding regions through top-down MS/MS, and correlate with fluorescence and transmission electron microscopy (TEM) measurements to understand target regions for aggregation inhibition mechanisms.