Abstract
Catalysis observed in enzymatic processes and protein polymerizations often relies on the use of supramolecular interactions and the organization of functional elements in order to gain control over the spatial and temporal elements of fundamental cellular processes. Harnessing these cooperative interactions to catalyse reactions in synthetic systems, however, remains challenging due to the difficulty in creating structurally controlled macromolecules. Here, we report a polypeptide-based macromolecule with spatially organized α-helices that can catalyse its own formation. The system consists of a linear polymeric scaffold containing a high density of initiating groups from which polypeptides are grown, forming a brush polymer. The folding of polypeptide side chains into α-helices dramatically enhances the polymerization rate due to cooperative interactions of macrodipoles between neighbouring α-helices. The parameters that affect the rate are elucidated by a two-stage kinetic model using principles from nucleation-controlled protein polymerizations; the key difference being the irreversible nature of this polymerization.
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Acknowledgements
The research was supported by the US National Science Foundation (CHE-1308485 and CHE-1508710 to J.C. & DMR-1150742 to Y.L.). AFM was carried out in part in the Frederick Seitz Materials Research Laboratory Central Research Facilities, University of Illinois.
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R.B., J.C. and Y.L. conceived the idea of the project. R.B. and Z.S. performed the experimental work. Y.L. and H.F. performed the kinetic modelling. R.B., Y.L., H.F., and J.C. wrote the manuscript with contributions from all authors. All authors discussed the results and commented on the manuscript.
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Baumgartner, R., Fu, H., Song, Z. et al. Cooperative polymerization of α-helices induced by macromolecular architecture. Nature Chem 9, 614–622 (2017). https://doi.org/10.1038/nchem.2712
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DOI: https://doi.org/10.1038/nchem.2712
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