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...

Amphiphilic Polyfluorinated Amino Ethers from Cyclic Sulfamidates

“…To further illustrate the potential of the method, we focused on ester-functionalized sulfamidates 1x and 1y that were prepared from l -serine ethyl and benzyl ester, respectively (Table ). The aim was to deliver nonproteogenic fluorinated amino acids that are important tools in the design of new peptide-based biomaterials. , In this context, we attempted to prepare β-OR F tertiary α-amino esters 2x and 2y , but it failed and only dehydroalanine elimination products 3x and 3y were isolated (Table ). The formation of such side products is a recurrent problem in the chemistry of sulfamidates that is caused by a competition between nucleophilic displacement and deprotonation of the α-hydrogen atom followed by elimination .…”

Fabrication of silk sericin–anthocyanin nanocoating for chelating and saturation-visualization detection of metal ions

“…Secondary structure is an essential characteristic of peptide and protein, 42 and monitoring the change of secondary structure can help understand the mechanism between SS and metal ions. As shown in Fig.…”

Fluorinated Protein and Peptide Materials for Biomedical Applications

“…They have the tendency to absorb considerable amounts of water within their network due to a presence of branched polar hydrophilic moieties, while maintaining their crosslinked structure in the swollen state. A pioneer in the field of fluorine chemistry, Koksch and her group have established broad principles governing the use of fluorine in peptide design to drive hydrogel self-assembly [ 83 ]. Crafting a library of dipeptides from a cationic scaffold comprised of the non-canonical AA homoalanine ( h A) also known as α-aminobutyric acid (Abu) and lysine, the group systematically varied the degree of fluorination to directly assess the impact of fluorine-specific interactions on self-assembling gelation behavior.…”

“…Monofluorinated, difluorinated, and trifluorinated γ-carbon derivatives of h A were synthetically incorporated to form the following 16-mer oligopeptides: MfeGlyK16, DfeGlyK16, and TfeGlyK16, which were all observed to form peptide hydrogels at physiological pH 7.4 ( Table 4 ). Investigating macroscopic mechanical properties, specifically the plateau storage moduli (G 0 ) which serves as a proxy of gel crosslinking density, the MfeGlyK16 gel was found to have the lowest G 0 value (0.53 Pa) compared to original scaffold constructed from non-fluorinated h A and lysine residues (4.81 Pa), which were both significantly lower than the difluorinated DfeGlyK16 (15.3 Pa) and trifluorinated TfeGlyK16 (670 Pa) [ 83 ]. These soft gels all display at least an order of magnitude less than the positive control of an analogous 16-mer comprised of repeating leucine and lysine dipeptides (4869 Pa), which the authors attribute to the higher degree of harmonious hydrophobicity displayed in the non-polar side chains [ 83 ].…”

“…Investigating macroscopic mechanical properties, specifically the plateau storage moduli (G 0 ) which serves as a proxy of gel crosslinking density, the MfeGlyK16 gel was found to have the lowest G 0 value (0.53 Pa) compared to original scaffold constructed from non-fluorinated h A and lysine residues (4.81 Pa), which were both significantly lower than the difluorinated DfeGlyK16 (15.3 Pa) and trifluorinated TfeGlyK16 (670 Pa) [ 83 ]. These soft gels all display at least an order of magnitude less than the positive control of an analogous 16-mer comprised of repeating leucine and lysine dipeptides (4869 Pa), which the authors attribute to the higher degree of harmonious hydrophobicity displayed in the non-polar side chains [ 83 ]. Thus, the successful addition of fluorine atoms to the scaffold seemed to strengthen hydrogel viscoelastic stability under physiological conditions, but not more than a rationally mutated hydrophobic residue, suggesting the fluorous effect to be less prominent than the hydrophobic effect in the self-assembly of peptide hydrogels.…”