Polypegylation of protein using semitelechelic and mid-functional poly(pegma)s synthesized by raft polymerization

Yingkai Liu, Mei Li, Dengxu Wang, Jinshui Yao, Jianxing Shen, Weiliang Liu, Shengyu Feng, Lei Tao, Thomas P Davis

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7 Citations (Scopus)


A series of well defined semitelechelic and mid-functionalized poly(poly(ethylene glycol) methyl ether methacrylate)s (poly(PEGMA)s) were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization using thiazolidine-2-thione-functionalized chain transfer agents (CTAs). The thiazolidine-2-thione group was located either at the end or in the middle of polymer chains depending on the different structural CTAs. All polymers were fully analyzed by 1H NMR spectroscopy and GPC, confirming their well-defined structures, such as predesigned molecular weights, narrow polydispersity indices, and high yield chain-end or chain-middle functionalization. The thiazolidine-2-thione functionality located at the end of or at the middle of the polymer chains can react with amine residues on protein surfaces, forming protein-polymer conjugates via amide linkages. The bioactivity of protein conjugates were subsequently tested using micrococcus lysodeikticus cell as substitute. The protein conjugations from the mid-functionalized polymer remained much more protein bioactivity comparing to their semitelechelic counterpart with similar molecular weights, indicating the steric hindrance of the mid-functionalized poly(PEGMA)s lead to the better selective conjugation to protein. The number of polymer chains on the protein surface was additionally evaluated by TNBS analysis, exhibiting that there are less mid-functionalized poly(PEGMA)s linked on the protein surface than the semitelechelic polymers, also supporting the hypothesis that the steric hindrance from branch-structural polymers results in the better reaction selectivity. This synthetic methodology is suitable for universal proteins, seeking a balance between the protein bioactivity and the protein protection by the covalent linkage with polymer, and exhibits promising potential for pharmaceutical protein conjugation. 

Original languageEnglish
Pages (from-to)1602-1610
Number of pages9
JournalAustralian Journal of Chemistry
Issue number12
Publication statusPublished - 2011
Externally publishedYes

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