Influence of Hydrophobic Face Amino Acids on the Hydrogelation of β-Hairpin Peptide Amphiphiles

Hydrophobic residues provide much of the thermodynamic driving force for the folding, self-assembly, and consequent hydrogelation of amphiphilic β-hairpin peptides. We investigate how the identity of hydrophobic side chains displayed from the hydrophobic face of these amphiphilic peptides influences their behavior to expound on the design criteria important to gel formation. Six peptides were designed that globally incorporate valine, aminobutyric acid, norvaline, norleucine, phenylalanine, or isoleucine on the hydrophobic face of the hairpin to study how systematic changes in hydrophobic content, β-sheet propensity, and aromaticity affect gelation. Circular dichroism (CD) spectroscopy indicates that hydrophobic content, rather than β-sheet propensity, dictates the temperature- and pH-dependent folding and assembly behavior of these peptides. Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) show that the local morphology of the fibrils formed via self-assembly is little aff...