Self-assembly of Fmoc-tetrapeptides based on the RGDS cell adhesion motif

Abstract

Self-assembly in aqueous solution has been investigated for two Fmoc [Fmoc = N-(fluorenyl)-9-methoxycarbonyl] tetrapeptides comprising the RGDS cell adhesion motif from fibronectin or the scrambled sequence GRDS. The hydrophobic Fmoc unit confers amphiphilicity on the molecules, and introduces aromatic stacking interactions. Circular dichroism and FTIR spectroscopy show that the self-assembly of both peptides at low concentration is dominated by interactions among Fmoc units, although Fmoc-GRDS shows β-sheet features, at lower concentration than Fmoc-RGDS. Fibre X-ray diffraction indicates β-sheet formation by both peptides at sufficiently high concentration. Strong alignment effects are revealed by linear dichroism experiments for Fmoc-GRDS. Cryo-TEM and small-angle X-ray scattering (SAXS) reveal that both samples form fibrils with a diameter of approximately 10 nm. Both Fmoc-tetrapeptides form self-supporting hydrogels at sufficiently high concentration. Dynamic shear rheometry enabled measurements of the moduli for the Fmoc-GRDS hydrogel, however syneresis was observed for the Fmoc-RGDS hydrogel which was significantly less stable to shear. Molecular dynamics computer simulations were carried out considering parallel and antiparallel β-sheet configurations of systems containing 7 and 21 molecules of Fmoc-RGDS or Fmoc-GRDS, the results being analyzed in terms of both intermolecular structural parameters and energy contributions.Postprint (published version

Hierarchical supramolecular hydrogels: self-assembly by peptides and photo-controlled release via host–guest interaction

“…Fibril structures were found in both cases and entanglement of fibers was also observed, which is consistent with reported literature. 27 In presence of Fmoc-RGDS-AAP, SEM showed more cross-linking fibers (Fig. 3) compared to only Fmoc-RGDS (Fig.…”

“…It has been reported that Fmoc-RGDS can form hydrogel and serve as cell adhesion motif. 27 The p-p interaction between hydrophobic…”

“…23,25 Different sequences of amino acids, used as hydrophilic head group, were optimized for various applications. 21,27,28 The Fmoc-protecting group is frequently applied as hydrophobic part since it is widely used in solid-phase peptide synthesis (SPPS). 21,22,29 Similar to polymeric hydrogels, the non-covalent interaction of peptide hydrogels also permits the development of multi-stimuli hydrogels.…”

“…In accordance with the literature, the selfassembled Fmoc-RGDS showed a disordered structure and a low signal at around 200 nm in the circular dichroism spectrum. 27 To further understand the thermal stability of the self-assembled peptide structure, spectra at different temperature were recorded. No change was observed in the spectra, suggesting that the self-assembled peptide is stable up to 45 1C (Fig.…”

Supramolecular Fmoc-valyl based nanoassemblies for delivery of mitoxantrone into HeLa cells

“…group being highly hydrophobic due to the presence of t-butyl carbamate group that is involved in hydrophobic interactions, allowing for the formation of gelatinous structures in aqueous solution [42][43]. Additionally, the presence of amide bonds allow for H-bonding interactions similar to natural peptide backbone between the -NH and C=O groups.…”