Sequence-encoded bioactive protein-multiblock polymer conjugates via quantitative one-pot iterative living polymerization

Ziying Li, Kaiyuan Song, Yu Chen, Qijing Huang, Lujia You, Li Yu, Baiyang Chen, Zihang Yuan, Yaqin Xu, Yue Su, Lintai Da (), Xinyuan Zhu and Ruijiao Dong ()
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Ziying Li: Shanghai Jiao Tong University
Kaiyuan Song: Shanghai Jiao Tong University
Yu Chen: Shanghai Jiao Tong University
Qijing Huang: Shanghai Jiao Tong University
Lujia You: Shanghai Jiao Tong University
Li Yu: Shanghai Jiao Tong University
Baiyang Chen: Shanghai Jiao Tong University
Zihang Yuan: Shanghai Jiao Tong University
Yaqin Xu: Shanghai Jiao Tong University
Yue Su: Shanghai Jiao Tong University
Lintai Da: Shanghai Jiao Tong University
Xinyuan Zhu: Shanghai Jiao Tong University
Ruijiao Dong: Shanghai Jiao Tong University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.

Date: 2024
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DOI: 10.1038/s41467-024-51122-1

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