State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Center of Pharmaceutical Technology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Molecules. 2022 Dec 13;27(24):8859. doi: 10.3390/molecules27248859.
Therapeutic proteins have unique advantages over small-molecule drugs in the treatment of various diseases, such as higher target specificity, stronger pharmacological efficacy and relatively low side effects. These advantages make them increasingly valued in drug development and clinical practice. However, although highly valued, the intrinsic limitations in their physical, chemical and pharmacological properties often restrict their wider applications. As one of the most important post-translational modifications, glycosylation has been shown to exert positive effects on many properties of proteins, including molecular stability, and pharmacodynamic and pharmacokinetic characteristics. Glycoengineering, which involves changing the glycosylation patterns of proteins, is therefore expected to be an effective means of overcoming the problems of therapeutic proteins. In this review, we summarize recent efforts and advances in the glycoengineering of erythropoietin and IgG monoclonal antibodies, with the goals of illustrating the importance of this strategy in improving the performance of therapeutic proteins and providing a brief overview of how glycoengineering is applied to protein-based drugs.
治疗性蛋白在治疗各种疾病方面具有优于小分子药物的独特优势，例如更高的靶标特异性、更强的药效学和相对较低的副作用。这些优势使得它们在药物开发和临床实践中越来越受到重视。然而，尽管受到高度重视，但它们在物理、化学和药理学性质方面的固有局限性常常限制了它们的更广泛应用。作为最重要的翻译后修饰之一，糖基化已被证明对蛋白质的许多性质（包括分子稳定性和药效学及药代动力学特征）具有积极影响。因此，糖基工程（涉及改变蛋白质的糖基化模式）有望成为克服治疗性蛋白问题的有效手段。在这篇综述中，我们总结了近年来在红细胞生成素和 IgG 单克隆抗体的糖基工程方面的努力和进展，旨在说明该策略在改善治疗性蛋白性能方面的重要性，并简要概述糖基工程如何应用于基于蛋白质的药物。
