细胞因子是一类由多种细胞产生的蛋白质或小分子多肽,具有生理活性强、免疫原性低、疗效高等优点,但其半衰期短,清除率高,易被人体降解。细胞因子类药物的不稳定性限制了其开发和应用,而导致该类药物不稳定的一个重要因素就是蛋白质(或多肽)特殊的分子结构。因此,对细胞因子的分子结构进行改造,是改变其理化性质和药代动力学性质的根本。本文从化学修饰、形成环肽及基因改造三方面对细胞因子类药物的分子改造作一综述。 Cytokines are a class of protein or small molecule peptides produced by a variety of cells. They have the advantages of strong physiological activity, low immunogenicity and high therapeutic effect. However, their short half-lives and high clearance rates are easily degraded by the human body. The instability of cytokines limits their development and application, and an important factor that leads to the instability of such drugs is the special molecular structure of protein (or polypeptide). Therefore, the molecular structure of cytokines to transform, is to change its physical and chemical properties and pharmacokinetic properties of the fundamental. This review summarizes the molecular modifications of cytokines from three aspects: chemical modification, formation of cyclic peptides and genetic modification.