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

Autor: Ziying Li, Kaiyuan Song, Yu Chen, Qijing Huang, Lujia You, Li Yu, Baiyang Chen, Zihang Yuan, Yaqin Xu, Yue Su, Lintai Da, Xinyuan Zhu, Ruijiao Dong
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-51122-1
Popis: 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.
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