Self-Assembly of Aromatic Amino Acid Enantiomers into Supramolecular Materials of High Rigidity

Abstract

Most natural biomolecules may exist in either of two enantiomeric forms. Although in nature, amino acid biopolymers are characterized by l-type homochirality, incorporation of d-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity, and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural, or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored. Herein, we investigated the self-assembly mechanism of amyloid-like structure formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan (Trp), both previously found as extremely important for the nucleation and self-assembly of aggregation-prone peptide regions into functional structures. Employing d-enantiomers, we demonstrate the critical role that amino acid chirality plays in their self-assembly process. The kinetics and morphology of pure enantiomers is completely altered upon their coassembly, allowing to fabricate different nanostructures that are mechanically more robust. Using diverse experimental techniques, we reveal the different molecular arrangement and self-assembly mechanism of the dl-racemic mixtures that resulted in the formation of advanced supramolecular materials. This study provides a simple yet sophisticated engineering model for the fabrication of attractive materials with bionanotechnological applications.

Highly Sensitive Polydiacetylene Ensembles for Biosensing and Bioimaging

“…Biomolecule self-assembling is highly implicated in various biologic events through a variety of non-covalent interactions, such as hydrophobic interaction, hydrogen bonds, electrostatic interaction, and metal coordination (Bera et al, 2020;Yu et al, 2020). The self-assembly structures are the basis of forming different complex biological structures (Cao et al, 2020).…”

Supramolecular Assembly and Chirality of Synthetic Carbohydrate Materials

“…[21] In particular, heterochiral peptide-based systems offer many advantages such as increased stiffness of the self-assembled fibers, [22] increased stability towards enzymatic degradation, [23] and access to new morphologies. [24] Inspired by this work, the enantiomeric disaccharide (LL) was synthesized starting from l-glucose (Supporting Information). Upon solvent switch, LL forms the enantiomeric helical fibers (right handed), confirming the direct correlation between oligosaccharide chirality and fiber helicity (Figure 3 A; Figure S11).…”

“…XRD confirmed that both enantiomers, DD(s) and LL(s), have identical crystallinity, whereas the racemic mixture packs in a different manner (Figure 3 B), as previously observed for heterochiral peptides assemblies. [24] Alteration of the 1:1 ratio between DD and LL creates irregularity in the structure, likely composed of flat structures and helical fibers ( Figure S13). AFM analysis of the flat aggregates (DD-LL(s)) suggests that the two enantiomers may construct a layer-by-layer supramolecular assembly (Figure 3 C).…”

“…Indeed, chirality is an important design mode in peptide nanotechnology [21] . In particular, heterochiral peptide‐based systems offer many advantages such as increased stiffness of the self‐assembled fibers, [22] increased stability towards enzymatic degradation, [23] and access to new morphologies [24] . Inspired by this work, the enantiomeric disaccharide ( LL ) was synthesized starting from L ‐glucose (Supporting Information).…”

Co-assembled Supramolecular Nanofibers With Tunable Surface Properties for Efficient Vaccine Delivery

“…Supramolecular hydrogels based on peptide self-assembly as potential nanocarriers have shown important applications in drug delivery, tissue engineering, cancer treatment and analysis (Wang et al, 2016a , 2018 , 2020a ; Yang et al, 2017 , 2020 ; Shigemitsu et al, 2018 ; Ren et al, 2019 ; Shang et al, 2019b ). Peptide monomolecules can self-assemble into specific nanostructures by non-covalent bonds including hydrophobic interaction, aromatic-aromatic stacking, hydrogen bond, etc., endowing them with ease of design, good biocompatibility and adjustable functions (Du et al, 2015 ; Chen et al, 2018 ; Shang et al, 2019a ; Yuan et al, 2019 ; Bera et al, 2020 ). In recent years, self-assembled peptides have been reported to exhibit immune-stimulating effects such as self-adjuvants.…”