Self‐assembly of short peptides composed of only aliphatic amino acids and a combination of aromatic and aliphatic amino acids

Abstract

The morphology of structures formed by the self-assembly of short N-terminal t-butyloxycarbonyl (Boc) and C-terminal methyl ester (OMe) protected and Boc-deprotected hydrophobic peptide esters was investigated. We have observed that Boc-protected peptide esters composed of either only aliphatic hydrophobic amino acids or aliphatic hydrophobic amino acids in combination with aromatic amino acids, formed highly organized structures, when dried from methanol solutions. Transmission and scanning electron microscopic images of the peptides Boc-Ile-Ile-OMe, Boc-Phe-Phe-Phe-Ile-Ile-OMe and Boc-Trp-Ile-Ile-OMe showed nanotubular structures. Removal of the Boc group resulted in disruption of the ability to form tubular structures though spherical aggregates were formed. Both Boc-Leu-Ile-Ile-OMe and H-Leu-Ile-Ile-OMe formed only spherical nanostructures. Dynamic light scattering studies showed that aggregates of varying dimensions were present in solution suggesting that self-assembly into ordered structures is facilitated by aggregation in solution. Fourier transform infrared spectroscopy and circular dichroism spectroscopy data show that although all four of the protected peptides adopt well-defined tertiary structures, upon removal of the Boc group, only H-Phe-Phe-Phe-Ile-Ile-OMe had the ability to adopt β-structure. Our results indicate that hydrophobic interaction is a very important determinant for self-assembly and presence of charged and aromatic amino acids in a peptide is not necessary for self-assembly.

Tunable Pentapeptide Self‐Assembled β‐Sheet Hydrogels

“…Experimental and computational approaches have yielded a selection of di‐ and tripeptide sequences,3, 4, 5, 6, 7 which have been proven to assemble into nanostructures and hydrogels under aqueous conditions, generating nanospheres,8 fibrous and plate‐like assemblies,9, 10 heterogeneous nanostructures,4, 11, 12 and micelles and nanotubes 13, 14, 15. To improve gelation characteristics, these small molecules often require either the inclusion of aromatic amino acid residues or a synthetic terminal group 1, 16, 17, 18, 19. This introduces π–π stacking and hydrophobic interactions, which promote self‐assembly and gelation 3.…”

Characterization of Silver and Fluorescent Dyes Incorporated in Self‐Assembling Peptides and Their Potential Applications in Biology

“…The inset shows uniformly dense spherical peptide nanostructures that also have the same morphology as that of the corresponding untreated peptide. [42] In some of these spherical peptide nanostructures, incorporation of Ag is only partial, as seen in Figure 1F, although the AgNPs appear to be all around the spherical peptide nanostructure as in Figure 1E, and therefore, it does not appear very dense.…”

“…By comparing the HPLC peak areas of peptides (both untreated and Ag-treated), the concentration of the peptides was calculated. These fractions were dried, the concentration adjusted to 5 mg mL À1 to form the nanostructures as described earlier, [42] and thereafter used for all the studies. In Boc-Ile-IleOMe···Ag and Boc-Leu-Ile-Ile-OMe···Ag, the dotted line denotes the peptide associated with Ag.…”

“…The Boc-Ile-Ile-OMe···Ag peptide exhibits dense tubular structures ( Figure 1C and D), the morphology of which is similar to the untreated peptide that we described earlier. [42] Boc-Leu-Ile-Ile-OMe···Ag displayed either totally or partially dark spherical nanostructures. In Fig-ure 1E, the AgNPs are not only seen studded around the peptide nanospheres, they also seem to have been incorporated into these structures that appear as dense particles.…”

“…[14] We have previously shown that short, hydrophobic, synthetic, N-terminal butyloxycarbonyl (Boc)-protected methyl esters of di-and tripeptides composed of only aliphatic amino acids (Boc-Ile-Ile-OMe and Boc-Leu-Ile-Ile-OMe) self-assembled into nanotubes and spherical nanoparticles, respectively, from solutions in methanol. [42] We investigated the interaction/incorporation, characterization, and application of these short peptide nanoparticles to examine whether they are good candidates for entrapment of small molecules and metals such as Ag, thus giving them the potential to be used as drug carriers and in diagnostics. In this study, we describe the incorporation of AgNPs into these nanostructures and characterize the physical and chemical properties by employing electron microscopy imaging techniques and various spectrometric methods.…”