Synthesis of polypeptides via bioinspired polymerization of in situ purified N-carboxyanhydrides

Ziyuan Song, Hailin Fu, Jiang Wang, Jingshu Hui, Tianrui Xue, Lazaro A. Pacheco, Haoyuan Yan, Ryan Baumgartner, Zhiyu Wang, Yingchun Xia, Xuefang Wang, Lichen Yin, Chongyi Chen, Joaquín Rodríguez-López, Andrew L. Ferguson, Yao Lin, Jianjun Cheng

Research output: Contribution to journalArticle

Abstract

Ribozymes synthesize proteins in a highly regulated local environment to minimize side reactions caused by various competing species. In contrast, it is challenging to prepare synthetic polypeptides from the polymerization of N-carboxyanhydrides (NCAs) in the presence of water and impurities, which induce monomer degradations and chain terminations, respectively. Inspired by natural protein synthesis, we herein report the preparation of welldefined polypeptides in the presence of competing species, by using a water/dichloromethane biphasic system with macroinitiators anchored at the interface. The impurities are extracted into the aqueous phase in situ, and the localized macroinitiators allow for NCA polymerization at a rate which outpaces water-induced side reactions. Our polymerization strategy streamlines the process from amino acids toward high molecular weight polypeptides with low dispersity by circumventing the tedious NCA purification and the demands for air-free conditions, enabling low-cost, largescale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials.

Original languageEnglish (US)
Pages (from-to)10658-10663
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume166
Issue number22
DOIs
StatePublished - 2019

Keywords

  • Bioinspired polymerization
  • In situ purification
  • N-carboxyanhydride
  • Polypeptide
  • Segregation

ASJC Scopus subject areas

  • General

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  • Cite this

    Song, Z., Fu, H., Wang, J., Hui, J., Xue, T., Pacheco, L. A., Yan, H., Baumgartner, R., Wang, Z., Xia, Y., Wang, X., Yin, L., Chen, C., Rodríguez-López, J., Ferguson, A. L., Lin, Y., & Cheng, J. (2019). Synthesis of polypeptides via bioinspired polymerization of in situ purified N-carboxyanhydrides. Proceedings of the National Academy of Sciences of the United States of America, 166(22), 10658-10663. https://doi.org/10.1073/pnas.1901442116