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Dynamic peptide libraries for the discovery of supramolecular nanomaterials

Abstract

Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

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Figure 1: Searchable dynamic peptide libraries.
Figure 2: Self-selecting peptide libraries of homodipeptides.
Figure 3: Sequence selection under user-defined conditions.
Figure 4: Self-selecting peptide libraries from heterodipeptide mixtures.
Figure 5: Discovery of peptide-based nanomaterials.

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Acknowledgements

The authors acknowledge P. Keating, S. Chakravartula and B. Yoo for the liquid chromatography–mass spectroscopy (LC–MS) experiments. We thank M. Mullin for the help with TEM imaging, N. T. Hunt for access to FTIR spectroscopy and S. Kelly for use of the CD equipment. The authors acknowledge the ‘NanoFabrication Facility’ from the CUNY ASRC. The authors also acknowledge R. Mart for the help with the design of the free-energy diagram (Fig. 1). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013) EMERgE/ERC (Grant Agreement Number 258775) and US Air Force (AFOSR, grant FA9550-15-1-0192). C.G.P. acknowledges Linn Products Ltd for funding and I.R.S. acknowledges the EC 7th Framework Programme Marie Curie Actions via the European ITN SMARTNET No. 316656.

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C.G.P., R.S., I.R.S and R.V.U. conceived and designed the experiments. C.G.P., R.S., I.R.S. and H.S. performed the experiments. C.G.P., R.S., I.R.S. and R.V.U. analysed the data. T.W. performed the TEM and cryo-TEM experiments. N.W. performed the rheological experiments. C.G.P. and V.N. performed the AFM experiments. R.A. performed the LC–MS experiments. C.G.P. and R.V.U. co-wrote the paper.

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Correspondence to Rein V. Ulijn.

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Pappas, C., Shafi, R., Sasselli, I. et al. Dynamic peptide libraries for the discovery of supramolecular nanomaterials. Nature Nanotech 11, 960–967 (2016). https://doi.org/10.1038/nnano.2016.169

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