The First Synthesis of Periodic and Alternating Glycopolymers by RAFT Polymerization: A Novel Synthetic Pathway for Glycosaminoglycan Mimics

Masahiko Minoda; Tomomi Otsubo; Yohei Yamamoto; Jianxin Zhao; Yoshitomo Honda; Tomonari Tanaka; Jin Motoyanagi

doi:10.3390/polym11010070

The First Synthesis of Periodic and Alternating Glycopolymers by RAFT Polymerization: A Novel Synthetic Pathway for Glycosaminoglycan Mimics

Polymers (Basel). 2019 Jan 5;11(1):70. doi: 10.3390/polym11010070.

Authors

Masahiko Minoda¹, Tomomi Otsubo², Yohei Yamamoto³, Jianxin Zhao⁴, Yoshitomo Honda⁵, Tomonari Tanaka⁶, Jin Motoyanagi⁷

Affiliations

¹ Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. minoda@kit.ac.jp.
² Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. m7618002@edu.kit.ac.jp.
³ Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. m5618030@edu.kit.ac.jp.
⁴ Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan. jianxinzhao@hotmail.com.
⁵ Institute of Dental Research, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan. honda-y@cc.osaka-dent.ac.jp.
⁶ Department of Biobased Materials Science, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. t-tanaka@kit.ac.jp.
⁷ Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. jinmoto@kit.ac.jp.

Abstract

This study concerned the controlled synthesis of periodic glycopolymers by reversible addition-fragmentation chain transfer (RAFT) copolymerization. To this end, maltose- and lactose-substituted vinyl ethers (MalVE and LacVE, respectively) and maltose-substituted maleimide (MalMI) were newly synthesized. RAFT copolymerization of MalVE and ethyl maleimide (EtMI) (monomer feed ratio: MalVE:EtMI = 1:1) afforded periodic glycopolymers (poly(MalVE-co-EtMI)) consisting of major parts of alternating structure (-(MalVE-EtMI)_n-) and a small part of consecutive sequences of EtMI (⁻EtMI-EtMI-). Occurrence of the latter sequences was caused by the homopolymerizability of maleimide under the present polymerization condition, and the formation of the consecutive sequences of EtMI was successfully suppressed by varying the monomer feed ratio. RAFT copolymerization of LacVE and EtMI was also found to proceed and similarly yielded periodic glycopolymers (poly(LacVE-co-EtMI)). Moreover, RAFT copolymerization of LacVE and MalMI (monomer feed ratio: LacVE:MalMI = 1:1) was performed to give copolymers (poly(LacVE-co-MalMI)) having composition ratio of LacVE/MalMI ≈ 36/64. The resultant periodic glycopolymers poly(MalVE-co-EtMI) and poly(LacVE-co-EtMI) were subjected to lectin binding assay using concanavalin A and peanut agglutinin, exhibiting the glycocluster effect. Moreover, these glycopolymers obtained from the copolymerization of VE and MI were found to be non-cytotoxic.

Keywords: CuAAC click reaction; RAFT copolymerization; alternating glycopolymer; carbohydrate-substituted maleimide; carbohydrate-substituted vinyl ether; glycosaminoglycan mimics; periodic glycopolymer.