Chemoenzymatic Polymerization of l-Serine Ethyl Ester in Aqueous Media without Side-Group Protection

Takumi Watanabe; Kayo Terada; Shogo Takemura; Hiroyasu Masunaga; Kousuke Tsuchiya; Alexandros Lamprou; Keiji Numata

doi:10.1021/acspolymersau.1c00052

Chemoenzymatic Polymerization of l-Serine Ethyl Ester in Aqueous Media without Side-Group Protection

ACS Polym Au. 2022 Jan 13;2(3):147-156. doi: 10.1021/acspolymersau.1c00052. eCollection 2022 Jun 8.

Authors

Takumi Watanabe¹, Kayo Terada¹, Shogo Takemura¹, Hiroyasu Masunaga², Kousuke Tsuchiya^{1

3}, Alexandros Lamprou⁴, Keiji Numata^{1

3}

Affiliations

¹ Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto Daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
² Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan.
³ Biomacromolecules Research Team, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
⁴ Innovation Campus Asia Pacific (Shanghai), BASF Advanced Chemicals Co., Ltd., No 300, Jiangxinsha Road, Pudong, Shanghai 200137, P.R. China.

Abstract

Poly(l-serine) (polySer) has tremendous potential as a polypeptide-based functional material due to the utility of the hydroxyl group on its side chain; however, tedious protection/deprotection of the hydroxyl groups is required for its synthesis. In this study, polySer was synthesized by the chemoenzymatic polymerization (CEP) of l-serine ethyl ester (Ser-OEt) or l-serine methyl ester (Ser-OMe) using papain as a catalyst in an aqueous medium. The CEP of Ser-OEt proceeded at basic pH ranging from 7.5 to 9.5 and resulted in the maximum precipitate yield of polySer at an optimized pH of 8.5. A series of peaks detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the formed precipitate consisted of polySer with a degree of polymerization ranging from 5 to 22. Moreover, infrared spectroscopy, circular dichroism spectroscopy, and synchrotron wide-angle X-ray diffraction measurements indicated that the obtained polySer formed a β-sheet/strand structure. This is the first time the synthesis of polySer was realized by CEP in aqueous solution without protecting the hydroxyl group of the Ser monomer.