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Shape-specific nanostructured protein mimics from de novo designed chimeric peptides

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Abstract

Natural proteins self-assemble into highly-ordered nanoscaled architectures to perform specific functions. The intricate functions of proteins have provided great impetus for researchers to develop strategies for designing and engineering synthetic nanostructures as protein mimics. Compared to the success in engineering fibrous protein mimetics, the design of discrete globular protein-like nanostructures has been challenging mainly due to the lack of precise control over geometric packing and intermolecular interactions among synthetic building blocks. In this contribution, we report an effective strategy to construct shape-specific nanostructures based on the self-assembly of chimeric peptides consisting of a coiled coil dimer and a collagen triple helix folding motif. Under salt-free conditions, we showed spontaneous self-assembly of the chimeric peptides into monodisperse, trigonal bipyramidal-like nanoparticles with precise control over the stoichiometry of two folding motifs and the geometrical arrangements relative to one another. Three coiled coil dimers are interdigitated on the equatorial plane while the two collagen triple helices are located in the axial position, perpendicular to the coiled coil plane. A detailed molecular model was proposed and further validated by small angle X-ray scattering experiments and molecular dynamics (MD) simulation. The results from this study indicated that the molecular folding of each motif within the chimeric peptides and their geometric packing played important roles in the formation of discrete protein-like nanoparticles. The peptide design and self-assembly mechanism may open up new routes for the construction of highly organized, discrete self-assembling protein-like nanostructures with greater levels of control over assembly accuracy.

Graphical abstract: Shape-specific nanostructured protein mimics from de novo designed chimeric peptides

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Publication details

The article was received on 06 Oct 2017, accepted on 09 Dec 2017 and first published on 11 Dec 2017


Article type: Paper
DOI: 10.1039/C7BM00906B
Citation: Biomater. Sci., 2018, Advance Article
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    Shape-specific nanostructured protein mimics from de novo designed chimeric peptides

    L. Jiang, S. Yang, R. Lund and H. Dong, Biomater. Sci., 2018, Advance Article , DOI: 10.1039/C7BM00906B

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