Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity

Abstract

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N···F charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

Self‐Assembled Artificial Ion‐Channels toward Natural Selection of Functions

“…More recently, Talukdar et al. discovered the importance of fluorination of the peptide backbones for their aggregation [86] . They reported that tripeptides with fluorine substituents presented a reverse‐turn U‐shaped conformation, whereas the non‐fluorinated counterparts only displayed disordered states.…”

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

“…Inspired by our recent ion transport studies with fluorinated acyclic and cyclic sugar derived peptides [17–18], we investigated the ion transport activity of 1 and 2a across lipid bilayer membranes. In this study, the collapse of the pH gradient (pH out = 7.8 and pH in = 7.0), created across egg yolk ʟ-α-phosphatidylcholine (EYPC) vesicles with entrapped 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) dye (i.e., EYPC-LUVsHPTS) [57–61] was monitored by measuring the fluorescence intensity of the dye at λ em = 510 nm (λ ex = 450 nm) with time (Figure S11, Supporting Information File 1).…”

“…Over the last several years, synthetic peptides are known to play a significant role in the design of artificial ion transport systems [13–16]. Recently, our group has synthesized fluorinated acyclic and cyclic peptides from C-3 fluorinated ᴅ-glucofuranoid amino acids and demonstrated their selective anion transport activity [17–18]. In continuation of our interest in sugar-derived cyclic peptides [19], we aimed to synthesize cyclic peptides I and II from the corresponding linear di- and tetrapeptides, however, we obtained an oxazolone ring containing pseudo peptides 1 and 2a, respectively (Fig.…”

Fluorinated peptide biomaterials

“…In separate work, backbone fluorination of cyclized tetra-and hexapeptides led to the formation of self-assembled nanotubes that serve as transmembrane anion-selective transporters. [36] Here, addition of fluorine atoms induced reverse turns that facilitated β-strand conformations and tubular assemblies, [36,72] for decades to promote and stabilize α-helical and β-hairpin conformations. [73][74][75][76] Similarly, phase-separated thin film electrodes have been realized by templating the assembly of an elastin-like peptide at the surface of a hydrophobic, perfluorinated ionomer.…”