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Cooperative polymerization of α-helices induced by macromolecular architecture

Nature Chemistry volume 9, pages 614–622 (2017)Cite this article

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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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Figure 1: Synthesis of linear and brush polypeptides.
Figure 2: Rate difference and kinetic pattern of NCA polymerization.
Figure 3: Kinetic studies of brush polymerization.
Figure 4: Kinetic studies of random and block macroinitiators.
Figure 5: Simulations with cooperative covalent polymerization model.
Figure 6: Analysis of brush polymerization with two-stage kinetic model.

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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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Authors and Affiliations

  1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Ryan Baumgartner & Jianjun Cheng

  2. Department of Chemistry and Institute of Materials Science, University of Connecticut, Storrs, 06269, Connecticut, USA

    Hailin Fu & Yao Lin

  3. Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Ziyuan Song & Jianjun Cheng

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  1. Ryan Baumgartner
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Contributions

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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Correspondence to Yao Lin or Jianjun Cheng.

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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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