2 research outputs found
The Impact of Halogenated Phenylalanine Derivatives on NFGAIL Amyloid Formation
The hexapeptide hIAPP22â27 (NFGAIL) is known as a crucial
amyloid core sequence of the human islet amyloid polypeptide
(hIAPP) whose aggregates can be used to better understand
the wild-type hIAPPâs toxicity to ÎČ-cell death. In amyloid
research, the role of hydrophobic and aromatic-aromatic
interactions as potential driving forces during the aggregation
process is controversially discussed not only in case of NFGAIL,
but also for amyloidogenic peptides in general. We have used
halogenation of the aromatic residue as a strategy to modulate
hydrophobic and aromatic-aromatic interactions and prepared
a library of NFGAIL variants containing fluorinated and
iodinated phenylalanine analogues. We used thioflavin T
staining, transmission electron microscopy (TEM) and smallangle
X-ray scattering (SAXS) to study the impact of side-chain
halogenation on NFGAIL amyloid formation kinetics. Our data
revealed a synergy between aggregation behavior and hydrophobicity
of the phenylalanine residue. This study introduces
systematic fluorination as a toolbox to further investigate the
nature of the amyloid self-assembly process