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随着生物药物的发展,蛋白质类药物在临床应用中具有越来越重要的作用。但是蛋白质药物也具有许多缺点。聚乙二醇是一种水溶性的高分子聚合物,对人体无毒副作用。用聚乙二醇对蛋白质药物进行修饰可以提高蛋白质药物的水溶性、降低免疫原性、延长半衰期、减少蛋白酶水解、提高稳定性等。传统的聚乙二醇修饰剂主要对蛋白质中的氨基进行修饰,修饰产物的均一性低、活性较差。而蛋白质聚乙二醇定点修饰技术针对蛋白质中特定的基团进行修饰,能够得到均一性高、活性高的产物,并且能够简化产物分离纯化的步骤,因此,近年来,蛋白质聚乙二醇定点修饰技术在生物化学领域得到广泛应用。文章概述了近年来聚乙二醇修饰剂的种类以及聚乙二醇定点修饰蛋白质药物的研究进展。
With the development of biopharmaceuticals, protein drugs play an increasingly important role in clinical application. But protein drugs also have many disadvantages. Polyethylene glycol is a water-soluble polymer, non-toxic side effects. Modification of protein drugs with polyethylene glycol can improve the water solubility of protein drugs, reduce immunogenicity, prolong half-life, reduce proteolytic hydrolysis and improve stability. The traditional polyethylene glycol modifier mainly modifies the amino group in the protein. The modification product has low homogeneity and poor activity. The modification of protein polyethylene glycol (PEG) for the specific groups in protein can get the products with high homogeneity and high activity, and can simplify the steps of product separation and purification. Therefore, in recent years, Modification techniques are widely used in the field of biochemistry. In this paper, the types of polyethylene glycol modifiers and the research progress of polyethylene glycol (PEG) site-directed modification of protein drugs are summarized.