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

CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
Journal of Peptide Science (Impact Factor: 1.86). 05/2012; 18(5):283-92. DOI: 10.1002/psc.2395
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing interest in studying the interaction of nanoparticles with biomolecules, microorganisms, and noble metals to explore their unique properties and potential biological applications. The synthetic butyloxycarbonyl (Boc)-protected methyl esters of peptides composed of only aliphatic amino acids (Boc-Ile-Ile-OMe and Boc-Leu-Ile-Ile-OMe) self-assembled into nanotubes and spheres, respectively, has been previously demonstrated. Herein, the characterization of these peptide nanoparticles incorporated with silver by means of various spectrometric methods and electron microscopy imaging techniques is described. The antibacterial activity of Ag-doped nanoparticles was determined. These peptide nanoparticles were demonstrated to be useful encapsulants of charged fluorescent dyes. This investigation demonstrates the potential of these short peptide nanoparticles to design formulations of antimicrobial agents that will enhance their activity and as fluorescent probes for cell imaging.
    ChemPlusChem 09/2014; 79(9). DOI:10.1002/cplu.201402077 · 3.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.
    Nature Chemistry 01/2015; DOI:10.1038/nchem.2122 · 23.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aromatic peptide amphiphiles are gaining popularity as building blocks for the bottom-up fabrication of nanomaterials, including gels. These materials combine the simplicity of small molecules with the versatility of peptides, with a range of applications proposed in biomedicine, nanotechnology, food science, cosmetics, etc. Despite their simplicity, a wide range of self-assembly behaviours have been described. Due to varying conditions and protocols used, care should be taken when attempting to directly compare results from the literature. In this review, we rationalise the structural features which govern the self-assembly of aromatic peptide amphiphiles by focusing on four segments, (i) the N-terminal aromatic component, (ii) linker segment, (iii) peptide sequence, and (iv) C-terminus. It is clear that the molecular structure of these components significantly influences the self-assembly process and resultant supramolecular architectures. A number of modes of assembly have been proposed, including parallel, antiparallel, and interlocked antiparallel stacking conformations. In addition, the co-assembly arrangements of aromatic peptide amphiphiles are reviewed. Overall, this review elucidates the structural trends and design rules that underpin the field of aromatic peptide amphiphile assembly, paving the way to a more rational design of nanomaterials based on aromatic peptide amphiphiles.
    Chemical Society Reviews 09/2014; 46(6). DOI:10.1039/c4cs00247d · 30.43 Impact Factor