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具有灵活对映体侧链的瓶刷聚合物显示出不同的生物特性
作者:小柯机器人 发布时间:2021/11/27 22:52:20

美国麻省理工学院Jeremiah A. Johnson、Rafael Gómez-Bombarelli等研究人员合作发现,具有灵活对映体侧链的瓶刷聚合物显示出不同的生物特性。相关论文于2021年11月25日在线发表在《自然—化学》杂志上。

研究人员利用迭代指数增长和开环异位聚合,从两个不同硬度的大分子对映体中产生水溶性的手性瓶刷聚合物(CBP)。值得注意的是,具有构象灵活的镜像侧链的CBP在细胞毒性、细胞摄取、血液药代动力学和肝脏清除方面显示出数倍的差异;具有相对刚性的镜像侧链的CBP则没有显示出任何差异。这些观察结果被一个简单的模型所合理化,该模型将更大的构象自由度与增强的手性识别联系起来。总之,这项工作提供了合成手性纳米结构聚合物的途径,并提出了立体化学和构象刚性在未来生物材料设计中的关键作用。

据介绍,手性和分子构象是生命的核心组成部分:生物系统依赖于离散(大)分子构象之间的立体相互作用,立体化学和刚性对小分子和生物大分子特性的影响已被深入研究。然而,这些特征如何影响合成大分子的特性却很少受到关注。

附:英文原文

Title: Bottlebrush polymers with flexible enantiomeric side chains display differential biological properties

Author: Nguyen, Hung V.-T., Jiang, Yivan, Mohapatra, Somesh, Wang, Wencong, Barnes, Jonathan C., Oldenhuis, Nathan J., Chen, Kathleen K., Axelrod, Simon, Huang, Zhihao, Chen, Qixian, Golder, Matthew R., Young, Katherine, Suvlu, Dylan, Shen, Yizhi, Willard, Adam P., Hore, Michael J. A., Gmez-Bombarelli, Rafael, Johnson, Jeremiah A.

Issue&Volume: 2021-11-25

Abstract: Chirality and molecular conformation are central components of life: biological systems rely on stereospecific interactions between discrete (macro)molecular conformers, and the impacts of stereochemistry and rigidity on the properties of small molecules and biomacromolecules have been intensively studied. Nevertheless, how these features affect the properties of synthetic macromolecules has received comparably little attention. Here we leverage iterative exponential growth and ring-opening metathesis polymerization to produce water-soluble, chiral bottlebrush polymers (CBPs) from two enantiomeric pairs of macromonomers of differing rigidity. Remarkably, CBPs with conformationally flexible, mirror image side chains show several-fold differences in cytotoxicity, cell uptake, blood pharmacokinetics and liver clearance; CBPs with comparably rigid, mirror image side chains show no differences. These observations are rationalized with a simple model that correlates greater conformational freedom with enhanced chiral recognition. Altogether, this work provides routes to the synthesis of chiral nanostructured polymers and suggests key roles for stereochemistry and conformational rigidity in the design of future biomaterials.

DOI: 10.1038/s41557-021-00826-8

Source: https://www.nature.com/articles/s41557-021-00826-8

期刊信息

Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:21.687
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex