Issue 28, 2022

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

Abstract

Advanced peptide-based nanomaterials composed of self-assembling peptides (SAPs) are of emerging interest in pharmaceutical and biomedical applications. The introduction of fluorine into peptides, in fact, offers unique opportunities to tune their biophysical properties and intermolecular interactions. In particular, the degree of fluorination plays a crucial role in peptide engineering as it can be used to control the characteristics of fluorine-specific interactions and, thus, peptide conformation and self-assembly. Here, we designed and explored a series of amphipathic peptides by incorporating the fluorinated amino acids (2S)-4-monofluoroethylglycine (MfeGly), (2S)-4,4-difluoroethylglycine (DfeGly) and (2S)-4,4,4-trifluoroethylglycine (TfeGly) as hydrophobic components. This approach enabled studying the impact of fluorination on secondary structure formation and peptide self-assembly on a systematic basis. We show that the interplay between polarity and hydrophobicity, both induced differentially by varying degrees of side chain fluorination, does affect peptide folding significantly. A greater degree of fluorination promotes peptide fibrillation and subsequent formation of physical hydrogels in physiological conditions. Molecular simulations revealed the key role played by electrostatically driven intra-chain and inter-chain contact pairs that are modulated by side chain fluorination and give insights into the different self-organization behaviour of selected peptides. Our study provides a systematic report about the distinct features of fluorinated oligomeric peptides with potential applications as peptide-based biomaterials.

Graphical abstract: Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

Supplementary files

Article information

Article type
Paper
Submitted
25 Mar 2022
Accepted
21 Jun 2022
First published
22 Jun 2022
This article is Open Access
Creative Commons BY-NC license

Nanoscale, 2022,14, 10176-10189

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

S. Chowdhary, R. F. Schmidt, A. K. Sahoo, T. tom Dieck, T. Hohmann, B. Schade, K. Brademann-Jock, A. F. Thünemann, R. R. Netz, M. Gradzielski and B. Koksch, Nanoscale, 2022, 14, 10176 DOI: 10.1039/D2NR01648F

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