Self‐Assembly of Tetraphenylalanine Peptides

Abstract

Three different tetraphenylalanine (FFFF) based peptides that differ at the N‐ and C‐termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head‐to‐tail NH3+⋅⋅⋅−OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N‐fluorenylmethoxycarbonyl (Fmoc) protected FFFF self‐assembles into a variety of polymorphs: ultra‐thin nanoplates, fibrils, and star‐like submicrometric aggregates. DFT calculations indicate that Fmoc‐FFFF prefers a parallel rather than an antiparallel β‐sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc‐FFFF‐OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.

Self-assembly of diphenylalanine with preclick components as capping groups

“…25 Furthermore, theoretical calculations on small model complexes predicted an antiparallel -structure, which was in good agreement with FTIR spectra.…”

“…25 However, in the case of Poc-FF-N 3 , SEM and OM micrographs suggest a mechanism based on the formation of a few nucleation centres on the glass and polystyrene surfaces. These nuclei favour the growth of uniformly oriented microfibers, which are probably stabilized through specific hydrogen bonds.…”

“…25 Nevertheless, the stability of these dendritic microstructures was very poor, disappearing when the glass slip was manipulated for SEM observations. The substitution of glass slides substrates by plasma functionalized polystyrene significantly enhanced the stability of such dendritic morphologies.…”

“…35 In a recent work we examined the self-assembly of phenylalanine-based peptides capped with Fmoc and 9-fluorenylmethyl ester (OFm) as N-and C-terminal aromatic components, respectively. 25 These systems exhibit a very high concentration of aromatic groups, which results from the complete elimination of both the normally free basic (N-terminus) and acidic (C-terminus) ends. Accordingly, supramolecular selfassembled organizations were expected to be reached through - stacking interactions.…”

Hierarchical self-assembly of di-, tri- and tetraphenylalanine peptides capped with two fluorenyl functionalities: from polymorphs to dendrites

“…In opposition, Fmoc-FFFF organizes into a variety of polymorphs depending on the experimental conditions, which included ultra-thin nanoplates, fibrils and star-like submicrometric aggregates. 21 The applications of self-assembled peptides in the biomedical (e.g. as cargo to target delivery of drugs and genes, scaffolds in tissue engineering and regenerative biomedicine, and biosensors) and nanotechnological (e.g.…”