Rational self-assembled peptides

Unfortunately, the description of amyloid fibrils given above is simplistic since in vitro self-assembly of amyloid peptides and proteins yields polymorphic structures, as has been commonly observed in the past for other protein assemblies such as actin filaments (Millonig et al, 1988) and intermediate filaments (Herrmann and Aebi, 1999). On the one hand, assembly polymorphism complicates the characterization of fibril structure. On the other hand, it offers some insight into fibril formation. For this reason a more rational understanding of amyloid fibril formation at the molecular level is a key issue in the field of amyloidosis. 

The rational synthesis of peptide-based nanotubes by self-assembling of polypeptides into a supramolecular structure was demonstrated. This self-organization leads to peptide nanotubes, having channels of 0.8 nm in diameter and a few hundred nanometer long (68). The connectivity of the proteins in these nanotubes is provided by weak bonds, like hydrogen bonds. These structures benefit from the relative flexibility of the protein backbone, which does not exist in nanotubes of covalently bonded inorganic compounds. 

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. 

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. 

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... 

Boden, N., Aggeli, A., Ingham, E., and Kirkham, J. Supramolecular Networks Made by Beta-Sheet Self-Assembly of Rationally Designed Peptides, and Their Uses as Industrial Fluids, Personal Care Products, Tissue Engineering Scaffolds and Drug Delivery Systems, 2003-GB3016 WO 2004007532 (2004). 

As an illustration of the second approach to biosynthesis, the work of Boden et al. will be taken as an example. Again the first step is to identify an interesting motif to be incorporated in a molecule. The motif that they have focussed on is the P-sheet. By incorporating a sequence which facilitates the formation of this structure it becomes possible to form a peptide which spontaneously self-assembles into P-sheet tapes. In appropriate solvents these peptides can form gels whose rheological properties can then be controlled by external parameters such as pH. Thus, what they have termed rational design coupled with the peptide synthesiser may yield macromolecules with a specific set of controlled properties. 

The rational synthesis of peptide-based nanotubes by self-assembling of polypeptides into a supramolecular structures was demonstrated. This self-organization leads... 

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