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

Abstract

Homopeptides with 2, 3 and 4 phenylalanine (Phe) residues and capped with fluorenylmethoxycarbonyl and fluorenylmethyl ester at the N-and C-terminus, respectively, have been synthesized to examine their self-assembly capabilities.Depending on the conditions, the di-and triphenylalanine derivatives self-organize into a wide variety of stable polymorphic structures, which have been characterized: stacked braids, doughnuts-like, bundled arrays of nanotubes, corkscrew-like and spherulitic microstructures. These highly aromatic Phe-based peptides also form incipient branched dendritic microstructures, even though they are highly unstable, making their manipulation very difficult. In opposition, the tetraphenylalanine derivative spontaneously self-assemble into stable dendritic microarchitectures made of branches growing from nucleated primary frameworks. The fractal dimension of these microstructures is 1.70, which evidences self-similarity and two-dimensional diffusion controlled growth. DFT calculations at the M06L/6-31G(d) level have been carried out on model -sheets since it is the most elementary building block of Phe-based peptide polymorphs. Results indicate that the antiparallel -sheet is more stable than the parallel one, the difference between them growing with the number of Phe residues. Thus, the cooperative effects associated with the antiparallel disposition become more favorable when the number of Phe residues increases from 2 to 4, while those of the parallel disposition remained practically constant.3

Surface Mediated Hierarchical Assemblies of Highly Hydrophobic Phenylalanine‐Based Peptides

“…Our results indicate that initially the peptide organizes into nanofibers, as is frequently observed in highly aromatic F‐based peptides . After this stage, which is dominated by peptide⋅⋅⋅peptide interactions, a very large variety of polymorphs can be subsequently formed by regulating the strength and nature of peptide⋅⋅⋅surface interactions.…”

“…Fmoc‐FFF self‐assembles into hydrogels, whereas Fmoc‐FFFF results in the formation of nanoplates, fibrils, star‐like aggregates and ill‐defined nanospheres depending on the incubation conditions . Besides, the influence of the environmental conditions (i. e. solvent, co‐solvent, temperature and concentration) on the self‐assembly of FF, FFF and FFFF peptides capped with two fluorenyl functionalities has been recently reported …”

“…Analysis of the influence of environmental considerations in the self‐assembly of both F‐homopeptides and F‐containing amphiphiles has evidenced the very important role played by π‐π staking interactions in the overall self‐assembled structures. Moreover, the impact of aromatic hydrophobic interactions on the formed structures seems to be also dependent on the peptide sequence and the chemical structure of the N‐ and/or C‐terminus blocking groups .…”

The fully‐extended conformation in peptides and proteins

“…In contrast, nonadditive contributions were slightly lower for secondary structures stabilized by intermolecular H‐bonds, as for example the β‐sheet. [ ].…”

The Physical Properties and Self‐Assembly Potential of the RFFFR Peptide

“…The observed entanglement of the fibers into sphere‐like structures must then be an indication that the Arg residues are not completely sufficient to limit the self‐assembly to only one direction. Other peptides structures that form supramolecular structures include the closely related FF, FFF, and FFFF peptides each capped with two fluorenyl functionalities . These peptides form polymorphic and dendrite structures under different conditions.…”