Peptide scaffolds, self-assembling

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. 

Holmes TC, de Lacalle S, Su X et al (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci 97 6728-6733... 

Zhou M, Smith AM, Das AK et al (2009) Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. Biomaterials 30 2523-2530... 

Adamantane can be used to construct peptidic scaffolding and synthesis of artificial proteins. It has been introduced into different types of synthetic peptidic macrocycles, which are useful tools in peptide chemistry and stereochemistry studies and have many other applications as well. Introduction of amino acid-functionalized adamantane to the DNA nanostmctures might lead to construction of DNA-adamantane-amino acid nanostmctures with desirable stiffness and integrity. Diamondoids can be employed to constmct molecular rods, cages, and containers and also for utilization in different methods of self-assembly. In fact, through the development of self-assembly approaches and utilization of diamondoids in these processes, it would be possible to design and constmct novel nanostmctures for effective and specific carriers for each dmg. 

Figure 14.8 (Left) Primary sequence of peptide MAXI with /8-hairpin promoted intramolecular folding, leading to the reversible formation of self-assembled /8-sheets. (Right) Cryo-TEM image of self-assembled peptide scaffolds. Scale bar = 200 nm. Reprinted from Schneider et al. (2002). Copyright 2002 American Chemical Society.

In another case, PAs were designed to function as magnetic resonance imaging (MRI) contrast agents (Bull et al. 2005) by covalently linking the peptide portion to a derivative of l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid followed by chelation of Gd ions by this moiety. The PAs were modified such that self-assembly produce either nanofibers or spherical micelles. The application of this self-assembling system could be extended to noninvasive MRI of PA scaffolds in vivo. 

Chau Y, Luo Y, Cheung ACY, Nagai Y, Zhang SG, Kobler JB, Zeitels SM, Langer R (2008) Incorporation of a matrix metalloproteinase-sensitive substrate into self-assembling peptides as a model for biofunctional scaffolds. Biomaterials 29 1713-1719... 

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). 

Genove, E., Semino, C., and Zhang, S. Self-Assembling Peptides Incorporating Modifications, Method for Preparation and Use as Scaffolds in Tissue Engineering, 2004-US20549... 

Stupp, S.I., and Kessler, J.A. Self-Assembling Peptide Amphiphiles Generating Nanofiber Scaffolds for Encapsulation, Growth and Differentiation of Neurons for Therapeutic Uses, 2006-US2354 2006079036 (2006). 

Firth, A., Aggeli, A., Burke, J.L., Yang, X.B., and Kirkham, J. "Biomimetic self-assembling peptides as injectable scaffolds for hard tissue engineering". Nanomedicine 1(2), 189-199... 

Kirkham, J., Firth, A., Vernals, D., Boden, N., Robinson, C., Shore, R.C., Brookes, S.J., and Aggeli, A. "Self-assembling peptide scaffolds promote enamel remineralization". /. Dental Res. 86(5), 426M30 (2007). 

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