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Engineering responsive mechanisms to control the assembly of peptide-based nanostructures

, : Engineering responsive mechanisms to control the assembly of peptide-based nanostructures. Biochemical Society Transactions 37(Pt 4): 653-659

Complex biological machines arise from self-assembly on the basis of structural features programmed into sequence-specific macromolecules (i.e. polypeptides and polynucleotides) at the molecular level. As a consequence of the near-absolute control of macromolecular architecture that results from such sequence specificity, biological structural platforms may have advantages for the creation of functional supramolecular assemblies in comparison with synthetic polymers. Thus biological structural motifs present an attractive target for the synthesis of artificial nanoscale systems on the basis of relationships between sequence and supramolecular structure that have been established for native biological assemblies. In the present review, we describe an approach to the creation of structurally defined supramolecular assemblies derived from synthetic alpha-helical coiled-coil structural motifs. Two distinct challenges are encountered in this approach to materials design: the ability to recode the canonical sequences of native coiled-coil structural motifs to accommodate the formation of structurally defined supramolecular assemblies (e.g. synthetic helical fibrils) and the development of methods to control supramolecular self-assembly of these peptide-based materials under defined conditions that would be amenable to conventional processing methods. In the present review, we focus on the development of mechanisms based on guest-host recognition to control fibril assembly/disassembly. This strategy utilizes the latent structural specificity encoded within sequence-defined peptides to couple a conformational transition within the coiled-coil motifs to incremental changes in environmental conditions. The example of a selective metal-ion-induced conformational switch will be employed to validate the design principles.


PMID: 19614570

DOI: 10.1042/BST0370653

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