Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Chem Rev. 2022 Oct 26;122(20):15603-15671. doi: 10.1021/acs.chemrev.1c01032. Epub 2022 Sep 29.
Glycoconjugates are major constituents of mammalian cells that are formed covalent conjugation of carbohydrates to other biomolecules like proteins and lipids and often expressed on the cell surfaces. Among the three major classes of glycoconjugates, proteoglycans and glycoproteins contain glycans linked to the protein backbone amino acid residues such as Asn for -linked glycans and Ser/Thr for -linked glycans. In glycolipids, glycans are linked to a lipid component such as glycerol, polyisoprenyl pyrophosphate, fatty acid ester, or sphingolipid. Recently, glycoconjugates have become better structurally defined and biosynthetically understood, especially those associated with human diseases, and are accessible to new drug, diagnostic, and therapeutic developments. This review describes the status and new advances in the biological study and therapeutic applications of natural and synthetic glycoconjugates, including proteoglycans, glycoproteins, and glycolipids. The scope, limitations, and novel methodologies in the synthesis and clinical development of glycoconjugates including vaccines, glyco-remodeled antibodies, glycan-based adjuvants, glycan-specific receptor-mediated drug delivery platforms, ., and their future prospectus are discussed.
糖缀合物是哺乳动物细胞的主要成分,通过碳水化合物与其他生物分子(如蛋白质和脂质)的共价键连接而形成,通常表达在细胞表面。在三大类糖缀合物中,蛋白聚糖和糖蛋白含有与蛋白质骨架相连的聚糖,如天冬酰胺(Asn)连接的聚糖和丝氨酸/苏氨酸(Ser/Thr)连接的聚糖。在糖脂中,聚糖与甘油、多异戊二烯焦磷酸、脂肪酸酯或鞘脂等脂质成分相连。最近,糖缀合物在结构上的定义和生物合成方面的理解得到了改善,特别是与人类疾病相关的糖缀合物,并为新药、诊断和治疗的发展提供了可能。本文综述了天然和合成糖缀合物(包括蛋白聚糖、糖蛋白和糖脂)在生物学研究和治疗应用方面的现状和新进展。讨论了糖缀合物(包括疫苗、糖修饰抗体、糖基佐剂、糖特异性受体介导的药物递送平台等)的合成和临床开发的范围、局限性和新方法,以及它们的未来前景。