Aromatic Motifs Dictate Nanohelix Handedness of Tripeptides

Abstract

Self-assembly of peptides and amyloid fibrils offers an appealing approach for creating chiral nanostructures, which has promising applications in the fields of biology and materials science. Although numerous selfassembled chiral materials have been designed, the precise control of their twisting tendency and their handedness is still a challenge. Herein, we report the self-assembly of chiral nanostructures with precisely tailored architectures by changing the amino acid sequences of the peptides. We designed a series of self-assembling tripeptides bearing different L-amino acid sequences. The peptide with L-Phe-L-Phe sequence preferred to self-assemble into left-handed nanohelices, while with L-Phe-L-Trp right-handed nanohelices would be formed. Moreover, the diameter of the self-assembled nanohelices could be tailored by changing the terminal amino acids (His, Arg, Ser, Glu, and Asp). Circular dichroism (CD) and molecular dynamics simulations (MDSs) revealed that both of the right-and left-handed nanohelices formed by the tripeptides showed negative Cotton effects in the peptide adsorption region but exhibited nearly opposite CD Cotton effects in the aromatic regions. These results indicated that the handedness of the self-assembled helical nanofibers was not only determined by the chirality of the peptide backbone but also closely related to the aromatic stacking, hydrogen bonding and steric interactions induced by the side chains. The findings deepen our understanding on the chiral self-assembly of peptide and offer opportunities for the creation of highly functional chiral nanomaterials.

Effect of Stereochemistry on Chirality and Gelation Properties of Supramolecular Self‐Assemblies

“…However, it is still difficult to predict self‐assembled supramolecular chirality based on a known peptide sequence that contains more than one chiral center [15–17] . Recently, some intriguing investigations into the chiral amplification phenomenon have been reported [36–38] . For example, Xu and co‐workers investigated the self‐assembly chirality of three pairs of short tetrapeptide enantiomers and found that the handedness of the supramolecular nanofibrils was determined by the chirality of the hydrophilic Lys head at the C terminus, whereas the morphological handedness could not be changed by altering the molecular chirality of hydrophobic Ile residues [16] …”

Which Stereoinductor Is Better for Asymmetric Functionalization of α‐Amino Acids in a Nickel(II) Coordination Environment? Experimental and DFT Considerations

“…The 3D structure of a molecule is determined not only by its basic structural network, which is defined by covalent bonding, but also by noncovalent interactions. Intricate noncovalent interactions govern many areas of biology and chemistry, including the design of new materials and drugs . Weak noncovalent interactions encompass hydrogen bonding, dipole–dipole interactions, steric repulsion, and London dispersion forces.…”

Solvent‐Controlled Topological Evolution from Nanospheres to Superhelices

“…In addition, the big steric barrier of the indole side chain constituted could be attributed to the formation of right‐handed twisted nanofibers. [ 31 ] Understanding the mechanism of fibril formation could be helpful to understand the process happened on prion disease resulting from soluble spherical molecules to an insoluble fibrous aggregation state and enable a wide range of potential applications.…”

“…The occurrence of chirality inversion in H 2 O when tailoring tryptophan into phenylalanine demonstrated the vital role of indole-related π-π association, hydrogen bonding, and steric effects in dictating the supramolecular chirality. [31] Additionally, LPWM(o) and LPWM(m) (Scheme 1a), the isomeric molecules of LPWM, were obtained, in which the tryptophan was substituted at ortho-position and meta-position of benzene core, respectively. Their purity was determined by NMR in Figures S6 and S7, Supporting Information.…”