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陕西快乐十分基本走势:Synthesis of polypeptides via bioinspired polymerization of in situ purified N-carboxyanhydrides
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Biomacromolecules are synthesized in cells with high precision, although the cellular environment contains numerous molecules and species other than the building blocks. In contrast, even the state-of-the-art chemical synthesis of macromolecules is exclusively carried out under a specific condition containing only clean, essential starting materials to minimize side reactions. Inspired by ribozyme-catalyzed protein synthesis, we report here controlled polypeptide synthesis by nonpurified N-carboxyanhydride monomers in an oil/water biphasic system that mediates impurity segregation and enables very fast polymerization that outpaces competing side reactions.
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 well-defined 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, large-scale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials.
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Author contributions: Z.S. and J.C. designed research; Z.S., H.F., J.W., J.H., T.X., L.A.P., H.Y., R.B., Z.W., Y.X., X.W., L.Y., C.C., J.R.-L., A.L.F., Y.L., and J.C. performed research; Z.S., H.F., Y.L., and J.C. analyzed data; and Z.S., H.F., J.W., J.H., A.L.F., Y.L., and J.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1901442116/-/DCSupplemental.
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