Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037; email:
Genomics Research Center, Academia Sinica, Taipei, Taiwan, 115.
Annu Rev Biochem. 2016 Jun 2;85:599-630. doi: 10.1146/annurev-biochem-060614-034420. Epub 2016 Apr 25.
Glycoscience research has been significantly impeded by the complex compositions of the glycans present in biological molecules and the lack of convenient tools suitable for studying the glycosylation process and its function. Polysaccharides and glycoconjugates are not encoded directly by genes; instead, their biosynthesis relies on the differential expression of carbohydrate enzymes, resulting in heterogeneous mixtures of glycoforms, each with a distinct physiological activity. Access to well-defined structures is required for functional study, and this has been provided by chemical and enzymatic synthesis and by the engineering of glycosylation pathways. This review covers general methods for preparing glycans commonly found in mammalian systems and applying them to the synthesis of therapeutically significant glycoconjugates (glycosaminoglycans, glycoproteins, glycolipids, glycosylphosphatidylinositol-anchored proteins) and the development of carbohydrate-based vaccines.
糖科学研究受到生物分子中存在的聚糖复杂组成以及缺乏适合研究糖基化过程及其功能的便捷工具的严重阻碍。多糖和糖缀合物不是直接由基因编码的;相反,它们的生物合成依赖于碳水化合物酶的差异表达,导致糖型的异质混合物,每种糖型都具有独特的生理活性。为了进行功能研究,需要获得具有明确结构的物质,这可以通过化学和酶合成以及糖基化途径的工程来实现。本文综述了制备哺乳动物系统中常见聚糖的一般方法,并将其应用于治疗意义重大的糖缀合物(糖胺聚糖、糖蛋白、糖脂、糖基磷脂酰肌醇锚定蛋白)的合成和基于碳水化合物的疫苗的开发。