Poly(ethylene glycol)s (PEGs) are the most used polymers in biomedicine, and their so-called “stealth” effects are the “gold standard” for biomaterials. However, the polydispersity in regular PEGs hampers their biomedical application, especially in modification of small molecular drugs (SMDs). To address this issue, many synthetic strategies for monodisperse PEGs (M-PEGs) have recently been developed. More importantly, M-PEGs have been successfully employed to modify SMDs, and the crucial roles of M-PEGs in PEGylated SMDs have been discovered in many cases. Herein we summarize the strategies for the synthesis of M-PEGylated SMDs, including Movantik, NKTR-181, polidocanol, propofol, and camptothecin, and the important roles of M-PEGs in optimizing the physicochemical properties, bioavailability, and therapeutic efficacy of SMDs. M-PEGylation is a convenient and effective strategy to develop novel SMDs, especially on the basis of marketed drugs. This review may shed light on the rational design and efficient synthesis of new M-PEGylated SMDs.

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通过单分散聚乙二醇修饰小分子药物的药物开发

聚乙二醇（PEG）是生物医学中使用最多的聚合物，其所谓的“隐身”效应是生物材料的“金标准”。但是，常规PEG中的多分散性会阻碍其生物医学应用，尤其是在小分子药物（SMD）的改性中。为了解决该问题，最近已经开发了许多用于单分散PEG（M-PEG）的合成策略。更重要的是，M-PEG已成功用于修饰SMD，并且在许多情况下已发现M-PEG在PEG化SMD中的关键作用。本文概述了M-PEG化SMD的合成策略，包括Movantik，NKTR-181，多多酚，丙泊酚和喜树碱，以及M-PEG在优化SMD的理化性质，生物利用度和治疗功效方面的重要作用。M-PEG化是开发新型SMD的便捷有效策略，尤其是在市售药物的基础上。这项审查可能会阐明新M-PEG化SMD的合理设计和有效合成。