Materials Department, Materials Research Laboratory, and Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, United States.
Department of Chemistry, University of California, Irvine, Irvine, California 92697, United States.
J Am Chem Soc. 2022 Oct 26;144(42):19466-19474. doi: 10.1021/jacs.2c07859. Epub 2022 Oct 14.
Poly(ethylene glycol) (PEG) is an important and widely used polymer in biological and pharmaceutical applications for minimizing nonspecific binding while improving blood circulation for therapeutic/imaging agents. However, commercial PEG samples are polydisperse, which hampers detailed studies on chain length-dependent properties and potentially increases antibody responses in pharmaceutical applications. Here, we report a practical and scalable method to prepare libraries of discrete PEG analogues with a branched, nonlinear structure. These lipid-PEG derivatives have a monodisperse backbone with side chains containing a discrete number of ethylene glycol units (3 or 4) and unique functionalizable chain ends. Significantly, the branched, nonlinear structure is shown to allow for efficient nanoparticle assembly while reducing anti-PEG antibody recognition when compared to commercial polydisperse linear systems, such as DMG-PEG2000. By enabling the scalable synthesis of a broad library of graft copolymers, fundamental self-assembly properties can be understood and shown to directly correlate with the total number of PEG units, nature of the chain ends, and overall backbone length. These results illustrate the advantages of discrete macromolecules when compared to traditional disperse materials.
聚乙二醇（PEG）是一种在生物和制药应用中非常重要且广泛使用的聚合物，用于最小化非特异性结合，同时提高治疗/成像剂的血液循环。然而，商业 PEG 样品是多分散的，这阻碍了对链长依赖性性质的详细研究，并可能在制药应用中增加抗体反应。在这里，我们报告了一种实用且可扩展的方法，用于制备具有支化、非线性结构的离散 PEG 类似物文库。这些脂化 PEG 衍生物具有单分散的主链，侧链含有离散数量的乙二醇单元（3 或 4）和独特的可功能化链末端。重要的是，与商业多分散线性系统（如 DMG-PEG2000）相比，支化、非线性结构可实现高效的纳米颗粒组装，同时降低抗 PEG 抗体的识别。通过能够大规模合成广泛的接枝共聚物文库，可以理解基本的自组装性质，并发现它们与 PEG 单元的总数、链末端的性质以及整个主链长度直接相关。这些结果说明了与传统分散材料相比，离散大分子的优势。
