Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation. Issue 28 (7th July 2022)

• Record Type: Journal Article
• Authors: Chowdhary, Suvrat; Schmidt, Robert Franz; Sahoo, Anil Kumar; tom Dieck, Tiemo; Hohmann, Thomas; Schade, Boris; Brademann-Jock, Kerstin; Thünemann, Andreas F.; Netz, Roland R.; Gradzielski, Michael; Koksch, Beate
• Is Part Of: Nanoscale. Volume 14:Issue 28(2022)
• Page Start: 10176
• Page End: 10189
• Publication Date: 2022-07-07
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d2nr01648f
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The tremendous impact of fluorine-specific interactions on peptide folding and self-assembly was systematically studied. Therefore, the fluorinated aliphatic amino acids MfeGly, DfeGly and TfeGly were incorporated into an amphipathic peptide motif. 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 (2 S )-4-monofluoroethylglycine (MfeGly ), (2 S )-4, 4-difluoroethylglycine (DfeGly ) and (2 S )-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.