Coiled-coils with defined assembly properties are attractive materials for the manufacture of peptidebased hybrid nanomaterials. In tailoring such peptide assemblies, the incorporation of aromatic residues is increasingly being investigated due to their potential to deliver controllable functionalities, such as interaction with aromatic porphyrins, carbon nanotubes, or graphene. Aromatic residues have the potential to either destabilise or stabilise the α-helical peptide structure, depending on the quantity, type, combination, and position of these residues in the peptide chain. In this work, we used a known synthetic three heptad repeat peptide containing no aromatic residues as an α-helical template. We the... More
Coiled-coils with defined assembly properties are attractive materials for the manufacture of peptidebased hybrid nanomaterials. In tailoring such peptide assemblies, the incorporation of aromatic residues is increasingly being investigated due to their potential to deliver controllable functionalities, such as interaction with aromatic porphyrins, carbon nanotubes, or graphene. Aromatic residues have the potential to either destabilise or stabilise the α-helical peptide structure, depending on the quantity, type, combination, and position of these residues in the peptide chain. In this work, we used a known synthetic three heptad repeat peptide containing no aromatic residues as an α-helical template. We then substituted the aliphatic residues with two different types of aromatic residues (phenylalanine and tryptophan), varying their number, position, and combination in the peptide chain as a preliminary assessment of the impact on peptide architecture. Circular dichroism (CD) spectroscopy combined with coarse-grained (CG) and allatom (AA) molecular dynamics (MD) simulations was used to analyse the peptide structure and assembly. Aromatic residues that were designed to be within the hydrophobic core had more impact on self-assembly than those placed on the outer face of the coil. Tryptophan was seen to destabilise the α-helical structure more than phenylalanine, potentially due to steric hindrance and hydrogen-bonding interactions. Using atomic force microscopy (AFM) and supported by CG-MD simulation, substituting all phenylalanine residues with tryptophan appeared to completely destabilise fibril-formation propensity. Substituting tryptophan into the first heptad repeat was seen to have a greater impact on fibril formation compared to substitution into the third heptad repeat, suggesting the importance of sequence design. These results add to the body of knowledge used to inform the design of α-helical peptides when incorporating aromatic residues.
