Peptides, molecular self-assembly

In Nature, there are many examples of protein and peptide molecular self-assembly. Of the genetically engineered fibrous proteins, collagen, spider silks, and elastin have received attention due to their mechanical and biological properties which can be used for biomaterials and tissue engineering. 

The work reviewed here demonstrates the tremendous versatility, promise and importance of peptides as building blocks in molecular self-assembly. However, in order to fully harness their potential in nanotechnology, more systematic work... 

A number of research groups have taken up this challenge and have developed rationally designed peptides adopting coiled coil structures that self-assemble into more complex nanostmctures. As a dominating and perhaps the most practical form of nanostructures, nanofiber assembly serves to illustrate the hierarchical molecular self-assembly possible in these systems. 

Figure 14.10 Self-assembly of peptide-amphiphiles into nanofibers (a) a peptide amphi-phile molecule with five distinct regions designed for hydroxyapatite mineralization, (b) a schematic of molecular self-assembly, and (c) a negatively stain transmission electron microscopy image of the nanofibers. Reprinted from Hartgerink et al. (2001). Copyright 2001 American Association for the Advancement of Science.

Several laboratories have described systems by which synthetic linear peptide chains self-assemble into desirable secondary and tertiary structures. One self-assembly approach has been the creation of a peptide-amphiphile, whereby a peptide head group has the propensity to form a distinct structural element, while a lipophilic tail serves to align the peptide strands and induce secondary and tertiary structure formation, as well as providing a hydrophobic surface for self-association and/or interaction with other surfaces. The preparation of a dialkyl ester tail first involves the acid-catalyzed condensation of H-Glu-OH with the appropriate fatty acid alcohol to form the dialkyl ester of H-Glu-OH a typical example is shown in Scheme 7. The assembly of peptide-amphiphiles with mono- and dialkyl ester tails is shown in Scheme 8. A series of studies have demonstrated that triple-helical and a-helical protein-like molecular architecture is stabilized in the peptide-amphiphile 44,63-65 ... 

In order to achieve thorough fundamental understanding of bio molecular self-assembly, it is imperative to study ID tape-like self-assembly not only in bulk solution but also at interfaces. An example of a biologically relevant interface is that of the lipid bilayer. Systematic peptide-lipid studies have begun to offer an insight into the basic principles and mechanisms of interactions of selfassembling peptides with model lipid layers (Protopapa et al., 2006). 

Vauthey, S., Santoso, S., Gong, H., Watson, N., and Zhang, S. (2002), Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles, Proc. Nat. Acad. Sci. U. S. A., 99, 5355-5360. 

The very efficient non-covalent approach to nanotubes by molecular self-assembly of cyclic peptides is limited by the kinetic instability of the resulting constructs. An elegant solution to... 

Plausible lipid-like peptides prebiotic molecular self-assembly in water Shuguang Zhang... 

Peptides composed of various coded and noncoded amino acid residues self-assemble to form various types of supramolecular architectures, including supramolecular helices and sheets, nanotubes, nanorods, nanovesicles, and nanofibers. The higher-order self-assembly of supramolecular (3-sheets or supramolecular helices composed of short synthetic acyclic peptides leads to the formation of amyloid-like fibrils. Synthetic cyclic peptides were used in supramolecular chemistry as molecular scaffolding for artificial receptors, so as to host various chiral and achiral ions and other small neutral substrates. Cyclic peptides also self-assemble like their acyclic counterparts to form supramolecular structures, including hollow nanotubes. Self-assembling cyclic peptides can be served as artificial ion channels, and some of them exhibit potential antimicrobial activities against drug-resistant bacteria. 

Reches, M., Gazit, E., 2006. Molecular self-assembly of peptide nanostructures mechanism of association and potential uses. Curr. Nanosd. 2, 105—111. 

Zhao X, Pan F, Xu H et al (2010) Molecular self-assembly and applications of designer peptide amphiphiles. Chem Soc Rev 39 3480-3498... 

FIGURE 2.4.6 (a) Cancer cell death induced by molecular self-assembly of an enzyme-responsive supramolecular gelator and (b) molecular structures of A/-palmitoyl-Gly-Gly-Gly-His-Gly-Pro-Leu-Gly-Leu-Ala-Arg-Lys-CONH2 (ER-C16), A/-palmitoyl-Gly-Gly-Gly-His-Gly-Pro-Leu-Gly (G-C16), and Leu-Ala-Arg-Lys-CONH2 (peptide fragment) [87]. 

The polarity of chlorinated solvents can also play a role in affecting the product distribution of an olefin metathesis reaction. Clark and Ghadiri [8] observed that the macrocyclic peptide 10 self assembles by inter molecular H-bonding in nonpolar solvents. The cylindrical conformation that resulted did not allow for successful dimerization to occur between macrocycles. When the cyclization of the cyclic peptide 10 was conducted with Ru catalyst 12 in chloroform (Scheme 12.5), the chloroform was proposed to disrupt the H-bonding within molecules. The new conformation produced in solution with the CHClj proved conducive to ring closure. The cyclic dimer 11 was obtained in 65% isolated yield as a mixture of cisicis, transitrans, and cisitrans isomers. 

Non-covalent interactions play a leading role in controlling the secondary and tertiary structures of natural macromolecules such as peptides, polynucleotides and polysaccarides or, for example, to provide the double helix structure of DNA where the base pairing between guanine and cytosine takes place by means of a threefold H-bonding. However, it is only relatively recently that such interactions have been exploited in the molecular self-assembly of well-defined S5mthetic supramolecular structures and materials. 

Many natural biomolecules, like peptides and proteins, interact and self-assemble to form delicate structures that are associated with specific functions (33). Ligaments and hair, for example, are assembled from collagen and keratin, respectively. DNA transcription is initiated by self-assembly of transcription factors, RNA polymerase, and DNA. Systematic studies and analysis of these natural existing self-assembly systems provide insight into the chemical and structural principles of peptide self-assembly, which inspires the development of molecular self-assembly as a new approach for fabrication of novel supramolecular architectures. 

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