Peptide self-assembly

What are the fundamental physical and chemical principles that underpin peptide self-assembly ... 

In order to explore systematically the main principles that guide peptide self-assembly, a useful approach is to study model self-assembling peptides. In this way, the namral chemical and conformational complexity of biological peptides... 

These two studies in particular are important. They demonstrate that not only can Pn peptide self-assembly be adjusted by sequence modification to suit a particular ionic strength and pH (e.g. conditions found in vitro or in vivo) but that it can be also made reversible and responsive. This raises the possibility that these peptides can be used in drug delivery, or as therapeutics that self-assemble post-injection. 

The way that Pn peptides self-assemble is important for polypeptides and proteins amyloid-type structures are believed to have the same core stmcture, and in fact the propensity to self-assemble in this manner is hypothesized to be a general property of polypeptides [52]. It is therefore unsurprising that systems featuring this motif are common. In recent years, a push towards the use of peptide-based self-assembled materials has led to increasing interest in extending their functionality by derivatising them. 

In this case, the restriction of peptide self-assembly was both desired, and by design. More generally, when looking to modify peptides and retain their self-assembly, where modifications are incompatible with assembly, post-assembly strategies will be necessary. 

Yucel T, Micklitsch CM, Schneider JP et al (2008) Direct observation of early-time hydrogelation in beta-hairpin peptide self-assembly. Macromolecules 41 5763-5772... 

Lamm MS, Rajagopal K, Schneider JP et al (2005) Laminated morphology of nontwisting beta-sheet fibrils constructed via peptide self-assembly. J Am Chem Soc 127 16692-16700... 

Biancalana M, Makabe K, Koide A, Koide S (2009) Molecular mechanism of thioflavin-T binding to the surface of b-rich peptide self-assemblies. J Mol Biol 385(4) 1052-1063... 

Wu C, Biancalana M, Koide S, Shea JE (2009) Binding modes of thioflavin-T to the singlelayer beta-sheet of the peptide self-assembly mimics. J Mol Biol 394(4) 627-633... 

Cyclic peptides, self-assembly of, 24 59-60 Cyclic peroxides, 18 436, 447-448, 459 Cyclic poly(aliphatic disulfide)s, 23 712 Cyclic poly(disulfide)s, available information related to, 23 713 Cyclic polyethers, 12 658 chelating agents, 5 710 Cyclic reforming operations, 25 166 Cyclic sesquiterpenoids, biosynthetic routes to, 24 472 Cyclic siloxanes... 

Cejas MA, Kinney WA, Chen C, Leo GC, Tounge BA, Vinter JG, Joshi PP, Maryanoff BE. Collagen-related peptides self-assembly of short, single strands into a functional biomaterial of micrometer scale. J Am Chem Soc 2007 129 2202-2203. 

Zimenkov Y, Dublin SN, Ni R, Tu RS, Breedvild V, Apkarian RP, Conticello VP. Rational design of a reversible pH-responsive switch for peptide self-assembly. J Am Chem Soc 2006 128 6770-6771. 

Ghosh, I. and Chmielewski, J. (2004). Peptide self-assembly as a model of proteins in the pre-genomic world. Curr. Opin. Chem. Biol, 8, 640-4. 

The utilization of peptide self-assembly additionally allows control of structural parameters and the rational control of functionalities, which are displayed at the nanofiber surface. This makes the presentation of biological signals and thus the introduction of bioactivity feasible. Stupp and coworkers investigated the self-assembly of peptide-amphiphiles (Fig. 4) [87, 115], The resulting worm-like, cylindrical nanostructures consist of a hydrophobic core that is formed by the alkyl... 

The following papers focus mainly on various aspects associated with the self-assembly of peptides. Peptides are relatively short sequences of amino acids, typically less than 50. The limited number of residues brings simplicity but still allows for sufficient differentiation to study self-assembly in its various details. The compositional freedom of the primary molecule allows for a sufficiently rich hierarchical structure creation through aggregation of individual peptides into supramolecular constructs resulting in interesting materials. This chapter looks into relevant patent literature as a reflection of the state of the art of technology in peptide self-assembly. 

As much of the more relevant scientific literature will be referenced in the subsequent papers, it is worthwhile examining the associated patent literature on peptide self-assembly. Patents are pursued to protect intellectual capital with the aim of developing science and technology into a business proposition. In the last 5 years, about 100 patents have been granted in the peptide self-assembly field with focus on applications in the medical and pharmaceutical markets. 

While the aforementioned technologies focus either on bulk or on solid-phase assembly, a more recent innovation in peptide self-assembly has targeted the soft or fluid-fluid interface. Designer peptides of 7 amino acid "heptad repeats" can be reversibly triggered to fold into an a-helix conformation to organize both hydrophilic and hydrophobic faces, thus inducing surfactant-like structure. These peptide surfactants, however, interact with each other in the interfacial plane, through reversible metal-ion coordination... 

Experimental evidence of hierarchical peptide self-assembly in solution... 

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