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Title: | Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity |
Authors: | Rajan, Robin Suzuki, Yu Matsumura, Kazuaki |
Keywords: | zwitterionic polymers RAFT polymerization protein aggregation refolding hydrophobicity |
Issue Date: | 2018-04-24 |
Publisher: | Wiley-VCH |
Magazine name: | Macromolecular Bioscience |
Volume: | 18 |
Number: | 6 |
Start page: | 1800016 |
DOI: | 10.1002/mabi.201800016 |
Abstract: | We describe the synthesis of a zwitterionic polymer, poly-sulfobetaine (poly-SPB), which shows remarkable efficiency in the suppression of insulin aggregation. Hydrophobic modification of the polymer resulted in almost complete inhibition at very low polymer concentrations. Further studies revealed that these polymers facilitate the complete retention of insulin’s secondary structure, which is otherwise lost after incubation. Refolding studies showed that addition of polymers to pre-aggregated insulin sample lead to the refolding of denatured insulin, indicating their potential to facilitate the refolding of the denatured proteins. In addition, 2D NMR studies showed that the presence of hydrophobic poly-SPB alters the hydrophobic environment of insulin, which may suppress hydrophobic interactions that lead to aggregation. These results indicate the enormous potential of these polymers for suppressing insulin aggregation and provide significant insight into the complex mechanism of insulin protection by zwitterionic polymers. |
Rights: | (c) 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: Robin Rajan, Yu Suzuki, Kazuaki Matsumura, Macromolecular Bioscience, 18(6), 2018, 1800016, which has been published in final form at https://doi.org/10.1002/mabi.201800016. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
URI: | http://hdl.handle.net/10119/17045 |
Material Type: | author |
Appears in Collections: | c10-1. 雑誌掲載論文 (Journal Articles)
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