Capacity for increased surface area in the hydrophobic core of β‐sheet peptide bilayer nanoribbons

Abstract

Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble into β‐sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self‐assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac‐(XKXE)2‐NH2 peptides (X = hydrophobic residue). A series of Ac‐(XKXE)2‐NH2 peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1‐naphthylalanine [1‐Nal], 2‐naphthylalanine [2‐Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self‐assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac‐X1KFEFKFE‐NH2 and Ac‐(X1,5KFE)‐NH2 peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT‐IR) spectroscopy indicated β‐sheet formation for all variants. Self‐assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self‐assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac‐(XKXE)2‐NH2 peptides correlates to self‐assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self‐assembled amphipathic peptides as functional biomaterials.

Short Peptides Derived from a Block Copolymer-like Barnacle Cement Protein Self-Assembled into Diverse Supramolecular Structures

“…P6 roughly exhibits amphipathic features composed of alternating hydrophilic (T and K) and hydrophobic residues (G, L, I, and A). Considering that amphipathic peptides can fold into β-sheets and self-assemble into β-sheet bilayer nanoribbons via sidechain hydrophobic functionality, , and that P6 can also form β-sheets as well as twisted nanoribbons, we reasoned that P6 probably employs its amphipathic features for self-assembly. P4 self-assembles into helical nanofibers and unique microrings in a pH-dependent manner.…”

Anti-Colonization Effect of Au Surfaces with Self-Assembled Molecular Monolayers Functionalized with Antimicrobial Peptides on S. epidermidis

“…This lipophilicity change is compatible with the AMPs being covalently linked to the surface by the CuAAC reaction. There were small differences between the peptides themselves with the same hydrophobic amino acids, but the biphenylalanine peptides ( 2a – d ) showed an overall higher contact angle than the tryptophan peptides ( 1a – d ) due to biphenylalanine being more hydrophobic than tryptophan [ 39 ].…”

Self-Assembly and Electrical Conductivity of a New [1]benzothieno[3,2-b][1]-benzothiophene (BTBT)-Peptide Hydrogel

“…In aqueous media, two sheets may self-assemble to form a β-sheet bilayer in which hydrophobic residues are buried inside, while the hydrophilic faces are exposed to the solvent. It has been demonstrated that this type of self-assembly can accommodate large aromatic side-chains in the inner shielded region and that increasing the area of the aromatic surface leads to stronger π-π interactions [ 37 ]. Thus, we expected to obtain self-assembled nanostructures with an aromatic core in which strong π-π interactions are established between BTBT chromophores.…”