RESUMO
Amphipathic peptides with alternating polar and nonpolar amino acid sequences efficiently self-assemble into functional ß-sheet fibrils as long as the nonpolar residues have sufficient hydrophobicity. For example, the Ac-(FKFE)2 -NH2 peptide rapidly self-assembles into ß-sheet bilayer nanoribbons, while Ac-(AKAE)2 -NH2 fails to self-assemble under similar conditions due to the significantly reduced hydrophobicity and ß-sheet propensity of Ala relative to Phe. Herein, we systematically explore the effect of substituting only two of the four Ala residues at various positions in the Ac-(AKAE)2 -NH2 peptide with amino acids of increasing hydrophobicity, ß-sheet potential, and surface area (including Phe, 1-naphthylalanine (1-Nal), 2-naphthylalanine (2-Nal), cyclohexylalanine (Cha), and pentafluorophenylalanine (F5 -Phe)) on the self-assembly propensity of the resulting sequences. It was found that double Phe variants, regardless of the position of substitution, failed to self-assemble under the conditions used in this study. In contrast, all double 1-Nal and 2-Nal variants readily self-assembled, albeit at differing rates depending on the substitution patterns. To determine whether this was due to hydrophobicity or side chain surface area, we also prepared double Cha and F5 -Phe variant peptides (both side chain groups are more hydrophobic than Phe). Each of these variants also underwent effective self-assembly, with the aromatic F5 -Phe peptides doing so with greater efficiency. These findings provide insight into the role of amino acid hydrophobicity and sequence pattern on self-assembly proclivity of amphipathic peptides and on how targeted substitutions of nonpolar residues in these sequences can be exploited to tune the characteristics of the resulting self-assembled materials.