Efficient Convergent Synthesis of Bi-, Tri-, and Tetra-antennary Complex Type N-Glycans and Their HIV-1 Antigenicity

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• 作者：Sachin S. Shivatare ; Shih-Huang Chang ; Tsung-I Tsai ; Chien-Tai Ren ; Hong-Yang Chuang ; Li Hsu ; Chih-Wei Lin ; Shiou-Ting Li ; Chung-Yi Wu ; Chi-Huey Wong
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：October 16, 2013
• 年：2013
• 卷：135
• 期：41
• 页码：15382-15391
• 全文大小：595K
• 年卷期：v.135,no.41(October 16, 2013)
• ISSN：1520-5126

文摘

The structural diversity of glycoproteins often comes from post-translational glycosylation with heterogeneous N-glycans. Understanding the complexity of glycans related to various biochemical processes demands a well-defined synthetic sugar library. We report herein a unified convergent strategy for the rapid production of bi-, tri-, and tetra-antennary complex type N-glycans with and without terminal N-acetylneuraminic acid residues connected via the 伪-2,6 or 伪-2,3 linkages. Moreover, using sialyltransferases to install sialic acid can minimize synthetic steps through the use of shared intermediates to simplify the complicated procedures associated with conventional sialic acid chemistry. Furthermore, these synthetic complex oligosaccharides were compiled to create a glycan array for the profiling of HIV-1 broadly neutralizing antibodies PG9 and PG16 that were isolated from HIV infected donors. From the study of antibody PG16, we identified potential natural and unnatural glycan ligands, which may facilitate the design of carbohydrate-based immunogens and hasten the HIV vaccine development.