随着基因和蛋白质工程的快速发展,蛋白质和肽已成为治疗应用的有希望的药物分子。因此,人们对化学修饰技术领域越来越感兴趣,以应对与临床使用相关的挑战,包括从循环中快速清除,免疫原性,物理和化学不稳定性(如聚集,吸附,脱氨,裁剪,氧化,等。),和酶降解。聚乙二醇(PEG)改性由于其有利的性质而为这些问题提供了有效的解决方案。本文综述了近年来聚乙二醇化治疗性蛋白和肽(TPPs)的开发和应用进展。为此,首先,介绍了PEG及其衍生物的理化性质和分类。随后,详细总结了PEG化TPP的主要位点和影响其PEG化的因素。此外,PEG修饰的TPP(包括抗菌肽(AMP),干扰素,天冬酰胺酶和抗体)突出显示。最后,我们建议用PEG对TPP进行化学修饰,分析了目前聚乙二醇化TPPs的发展现状和前景。这项工作在这个有前途的领域提供了全面的文献综述,同时促进了研究人员利用PEG聚合物修饰TPP进行疾病治疗。
With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their
PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.