Abstract

Amyloid peptides yield a plethora of interesting nanostructures though difficult to control. Here we report that depending on the number, position, and nature of the halogen atoms introduced into either one or both phenylalanine benzene rings of the amyloid β peptide-derived core-sequence KLVFF, four different architectures were obtained in a controlled manner. Our findings demonstrate that halogenation may develop as a general strategy to engineer amyloidal peptide self-assembly and obtain new amyloidal nanostructures.

Highlights

  • Andrea Pizzi, a Claudia Pigliacelli,b Alessandro Gori,c Nonappa, b Olli Ikkala, b Nicola Demitri,d Giancarlo Terraneo,a Valeria Castelletto,e Ian W

  • We report that depending on the number, position, and nature of the halogen atoms introduced into either one or both phenylalanine benzene rings of the amyloid β peptide-derived core-sequence KLVFF, four different architectures were obtained in a controlled manner

  • The chemical functionalization of the peptide sequence has been demonstrated to be a powerful tool for controlling amyloid self-assembly.[14,15]

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Summary

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By placing a halogen atom on the inner phenylalanine residue of the sequence, an amyloid hydrogel was obtained, while different discrete morphologies could have been achieved when the terminal phenylalanine was functionalized with a halogen atom Due to their interesting morphologies and to ascertain whether the observed peptide nanostructures may be related to drying effects, the vitrified 15 mM aqueous solutions of KLVFF(I) and KLVF(Br)F(Br) were further investigated by Cryogenic-TEM (Cryo-TEM). Bonding causes KLVF(I)F(I) monomers to pair in parallel mode, while in the structure of the non-iodinated sequence KLVFFA,[31] monomers pair in antiparallel mode, resulting in a different type of “steric zipper” (Fig. S15†) This result confirms the possibility to exploit the halogen bond as a tool to engineer the β-sheet and the self-assembly of amyloidal peptides.[17] The single-crystal structures of KLVF(Br)F(Br) and KLVF(Cl)F(Cl) were successfully determined. More detailed investigation on this mechanism will be reported in a separate research article

Conclusions
Dynamic light scattering
Transmission electron microscopy
Findings
Author contributions statement

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