Structural Polymorphism in a Self-Assembled Tri-Aromatic Peptide System

Abstract

Self-assembly is a process of key importance in natural systems and in nanotechnology. Peptides are attractive building blocks due to their relative facile synthesis, biocompatibility, and other unique properties. Diphenylalanine (FF) and its derivatives are known to form nanostructures of various architectures and interesting and varied characteristics. The larger triphenylalanine peptide (FFF) was found to self-assemble as efficiently as FF, forming related but distinct architectures of plate-like and spherical nanostructures. Here, to understand the effect of triaromatic systems on the self-assembly process, we examined carboxybenzyl-protected diphenylalanine (z-FF) as a minimal model for such an arrangement. We explored different self-assembly conditions by changing solvent compositions and peptide concentrations, generating a phase diagram for the assemblies. We discovered that z-FF can form a variety of structures, including nanowires, fibers, nanospheres, and nanotoroids, the latter were previously observed only in considerably larger or co-assembly systems. Secondary structure analysis revealed that all assemblies possessed a β-sheet conformation. Additionally, in solvent combinations with high water ratios, z-FF formed rigid and self-healing hydrogels. X-ray crystallography revealed a "wishbone" structure, in which z-FF dimers are linked by hydrogen bonds mediated by methanol molecules, with a 2-fold screw symmetry along the c-axis. All-atom molecular dynamics (MD) simulations revealed conformations similar to the crystal structure. Coarse-grained MD simulated the assembly of the peptide into either fibers or spheres in different solvent systems, consistent with the experimental results. This work thus expands the building block library for the fabrication of nanostructures by peptide self-assembly.

Unusual Two‐Step Assembly of a Minimalistic Dipeptide‐Based Functional Hypergelator

“…Simulations at low peptide concentrations, as experimentally used, are computationally intensive. In order to reduce the need of computational power and accelerate the assmebly process, we set the peptide concentrations in our simulations to be much higher, in accordence with previous simulation studies . Each Fmoc‐Lys(Fmoc)‐Asp molecule was modeled by 14 hydrophobic beads for the Fmoc groups, two negatively charged beads for the Asp group, and five beads for the Lys group (lysine is neutral).…”

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces

“…20 to 200 nm. 40,41 Note the thickness values were obtained by measuring the image with the ImageJ software, and therefore these values might be taken only as a semiquantitative approach. The apparent discrepancy between the two values of thickness was ascribed to the different conditions for measuring, e. g., the electron microscopy picture was taken under high vacuum and extremely low content of water, whereas the BAM pictures were taken in contact with the water surface in laboratory conditions.…”

Supramolecular Nanofibers of Drug‐Peptide Amphiphile and Affibody Suppress HER2+ Tumor Growth

“…We then used NBD‐βA‐G D F D Fp D Y (Figure , NBD represents 4‐Chloro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole, a fluorophore to track the distribution of peptides) to test its coassembled property with the affibody . Using the EISA process, the NBD‐βA‐G D F D Fp D Y could be converted to a hydrogelator NBD‐βA‐G D F D F D Y that would form supramolecular nanofibers and hydrogels . In the presence of affibody, the phosphate buffer saline (PBS) solution of NBD‐βA‐G D F D Fp D Y would also be converted to a hydrogel by alkali phosphatase (ALP, Figure ) .…”