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The Impact of Halogenated Phenylalanine Derivatives on NFGAIL Amyloid Formation

S. Chowdhary, J. Moschner, D. J. Mikolajczak, M. Becker, A. F. Thunemann, C. Kastner, D. Klemczak, A. K. Stegemann, C. Bottcher, P. Metrangolo, R. R. Netz and B. Koksch – 2020

The hexapeptide hIAPP22-27 (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 hIAPP's toxicity to beta-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 small-angle 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.

Titel
The Impact of Halogenated Phenylalanine Derivatives on NFGAIL Amyloid Formation
Verfasser
S. Chowdhary, J. Moschner, D. J. Mikolajczak, M. Becker, A. F. Thunemann, C. Kastner, D. Klemczak, A. K. Stegemann, C. Bottcher, P. Metrangolo, R. R. Netz and B. Koksch
Datum
2020
Kennung
DOI:10.1002/cbic.202000373
Zitierweise
Chembiochem 2020, 21 (24), 3544-3554
Sprache
eng
Art
Text