酶法精准合成活性类肝素寡糖  

Enzymatic methods for the precise synthesis of bioactive heparin-like oligosaccharides

作　　者：辛思语 徐美鑫 生举正 XIN Siyu;XU Meixin;SHENG Juzheng(School of Pharmaceutical Sciences,Shandong University,Ji’nan 250000,China;National Glycoengineering Research Center,Shandong University,Ji’nan 250000,China)

机构地区：[1]山东大学药学院,济南250000 [2]山东大学国家糖工程技术研究中心,济南250000

出　　处：《生命的化学》2024年第7期1192-1204,共13页Chemistry of Life

基　　金：国家重点研发计划项目(2023YFA0914300);山东省科技厅项目(2022SFGC0104)。

摘　　要：肝素是一类重要的人源直链硫酸化多糖,作为重要的抗凝血和治疗血栓性疾病的临床药物被广泛使用。近年来,肝素的糖链结构所蕴含的生物信息引起了广泛关注,其抗菌和抗炎等其他生物学功能也逐渐被揭示。然而,目前肝素类药物的生产主要依赖于动物组织提取,这导致了产品结构的异质性、潜在的污染风险以及质量控制的复杂性。此外,尽管全化学合成肝素的方法存在,但其合成过程繁琐,且合成的糖链长度有限,难以满足临床药物对结构多样性的需求。因此,通过酶促级联反应实现活性类肝素寡糖的精准合成,为解决当前肝素类药物面临的问题提供了一种有效的策略。本文系统综述了类肝素寡糖酶法合成体系的最新研究进展。Heparin represents a significant category of straight-chain sulfated polysaccharides derived from human sources.It is extensively utilized as a vital clinical medication for anticoagulation and the management of thrombotic disorders.Lately,there has been a surge of interest in the biological information encoded within the glycan chain of heparin,with its additional biological roles,including antimicrobial and anti-inflammatory properties,being progressively uncovered.However,the current methods for producing heparin analogs predominantly depend on extraction from animal tissues.This approach results in product structural heterogeneity,potential contamination risks,and intricate quality control challenges.Although there is an option for the total chemical synthesis of heparin,the arduous synthesis process and the restricted length of the glycan chains produced make it challenging to fulfill the clinical demand for structural diversity.Consequently,the precise synthesis of bioactive heparin-like oligosaccharides through enzymatic cascade reactions emerges as a viable strategy to address the issues currently encountered with heparin analogs.In this work,we provide a comprehensive review of the recent advancements in the enzymatic synthesis system for the creation of heparin-like oligosaccharides.

关 键 词：类肝素寡糖 酶法合成 结构确定 

分 类 号：TQ460.6[化学工程—制药化工]