Sequence-Dependent Nanofiber Structures of Phenylalanine and Isoleucine Tripeptides

Abstract

The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence–structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.

Multiscale, Multiresolution Coarse-Grained Model via a Hybrid Approach: Solvation, Structure, and Self-Assembly of Aromatic Tripeptides

“…Still another study reported nanofiber aggregates encompassing uncapped FFF. 12 Using different capping groups 13 such as tert-butyloxycarbonyl (Boc) group for the N terminal and carboxylic acid for the C terminal, the FFF derivative adopts a turnpike conformation and self-assembles into crystalline nanospheres which are thermally and chemical stable. FFF capped with two fluorenyl functionalities self-assembled into stacked braids which further formed corkscrew-like microstructures at higher peptide concentrations.…”

“…The results seemed to indicate that the FFF molecules adopt both parallel and antiparallel β-sheets, although the former is surmised to be energetically preferred due to the π–π stacking between the aromatic rings of molecules that have hydrogen bonding. Still another study reported nanofiber aggregates encompassing uncapped FFF …”

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…In particular, self-assembling short-peptides represent cheap building blocks for large-scale production, and with overall promising properties in terms of bioactivity [ 2 ] and biocompatibility to achieve functional materials [ 3 , 4 ]. The large chemical diversity they provide ensures continuous advancements, and even considering just the publications in the last couple of years, numerous regard self-assembling tripeptides [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] and dipeptides [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Furthermore, the study of such simple systems could advance the understanding of prebiotic chemistry, relative to the potential role of peptide-based organized structures in the emergence of catalytic activity [ 26 ].…”

Synthesis and Self-Assembly Properties of Bola-Amphiphilic Glycosylated Lipopeptide-Type Supramolecular Hydrogels Showing Colour Changes Along with Gel–Sol Transition

“…F2 peptide can self-assemble into a nanostructure that is obtained by combining hydrogen bonding and π - π stacking interactions. Despite the significant attention on F2-based hydrogels, a few examples of triphenylalanine (F3)- or tetraphenylalanine (F4)-based hydrogels and self-assembled nanostructures have been investigated [ 60 , 61 , 62 , 63 , 64 , 65 ]. Here, we evaluate the effects of the number of F residues on the gelation ability and the morphology of the self-assembled nanostructures.…”