Bioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, Singapore.
Bioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, Singapore.
Biomed Pharmacother. 2023 Jul;163:114757. doi: 10.1016/j.biopha.2023.114757. Epub 2023 Apr 21.
The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically modified by various means to enhance their circulatory half-life. One approach is to manipulate the N-glycan composition of these agents. Among the many glycan constituents, sialic acid (specifically, N-acetylneuraminic acid) plays a critical role in extending circulatory half-life by masking the terminal galactose that would otherwise be recognised by the hepatic asialoglycoprotein receptor (ASGPR), resulting in clearance of the biotherapeutic from the circulation. This review aims to provide an illustrative overview of various strategies to enhance the pharmacokinetic/pharmacodynamic properties of recombinant therapeutic proteins through manipulation of their sialic acid content.
重组治疗性蛋白的循环半衰期是一个重要的药代动力学属性，因为它决定了这些药物的给药频率，直接转化为治疗成本。因此，各种方法已被用于对重组治疗性糖蛋白（如单克隆抗体）进行化学修饰，以增强其循环半衰期。一种方法是操纵这些药物的 N-糖链组成。在众多糖链成分中，唾液酸（具体为 N-乙酰神经氨酸）通过掩盖末端半乳糖发挥关键作用，否则末端半乳糖会被肝脏的去唾液酸糖蛋白受体（ASGPR）识别，从而导致生物治疗剂从循环中清除。本综述旨在提供一个说明性的概述，介绍通过操纵重组治疗性蛋白的唾液酸含量来增强其药代动力学/药效学特性的各种策略。
