Discrete polyethylene glycol derivatives as a potent impetus for next-generation biomedicines
Discrete polyethylene glycol derivatives as a potent impetus for next-generation biomedicines
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DOI：
10.1016/j.giant.2023.100169
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发表时间：
2023-05-22
期刊：
影响因子：
7
通讯作者：
Liu，Shiyong
中科院分区：
文献类型：
--
作者：
Cen，Jie;Hou，Mingxuan;Liu，Shiyong
聚乙二醇化是利用聚乙二醇（PEG）对小分子药物、肽和蛋白质进行共价修饰，以改善其药代动力学和疗效，已成为最广泛使用的药物修饰技术之一。然而，PEG及其衍生物已被证实具有免疫原性和抗原性，这直接导致了诸如加速血液清除（ABC）现象以及对聚乙二醇化药物或聚乙二醇赋形剂的过敏反应等副作用。单分子量离散 PEG 合成方法的最新发展引起了人们对传统多分散 PEG 和单分子量精确 PEG 之间生物活性差异的持续和广泛关注。离散PEG在抵抗蛋白质吸附、细胞粘附和增强药效方面表现出明显的优势。这些初步结果不仅证实了PEG链多分散性对其生物学效应的显着影响，而且揭示了使用离散PEG降低免疫原性和抗原性的可能性和潜在优势。希望单一的化学结构和分子量能够确保新开发的离散PEG产品的批次重复性，并有助于了解其理化性质和生物效应，从而促进精准PEG药物的临床转化。
PEGylation, which covalently modifies small-molecule drugs, peptides and proteins with polyethylene glycol (PEG) to improve their pharmacokinetics and efficacy, has become one of the most widely used drug modification techniques. However, PEG and its derivatives have been verified to be immunogenic and antigenic, which directly lead to side effects such as accelerated blood clearance (ABC) phenomenon and allergic reactions to PEGylated drugs or PEG excipients. Recent development of single molecular weight discrete PEG synthesis methodology have led to continuous and extensive focus on the difference in biological activity between conventional polydisperse PEG and single molecular weight precise PEG. Discrete PEG has demonstrated obvious advantages in resisting protein adsorption, cell adhesion and enhancing drug efficacy. These preliminary results not only confirm the significant impact of PEG chain polydispersity on its biological effect, but also reveal the possibility and potential advantages of using discrete PEG to reduce the immunogenicity and antigenicity. Hopefully, single chemical structure and molecular weight ensure the batch repeatability of newly developed discrete PEG products, and facilitate the understanding of their physicochemical properties and biological effects that promoting the clinical conversion of precise PEG drugs.