Artificial Golgi Apparatus: Globular Protein-like Dendrimer Facilitates Fully Automated Enzymatic Glycan Synthesis

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• 作者：Takahiko Matsushita ; Izuru Nagashima ; Masataka Fumoto ; Takashi Ohta ; Kuriko Yamada ; Hiroki Shimizu ; Hiroshi Hinou ; Kentaro Naruchi ; Takaomi Ito ; Hirosato Kondo ; Shin-Ichiro Nishimura
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：November 24, 2010
• 年：2010
• 卷：132
• 期：46
• 页码：16651-16656
• 全文大小：354K
• 年卷期：v.132,no.46(November 24, 2010)
• ISSN：1520-5126

文摘

Despite the growing importance of synthetic glycans as tools for biological studies and drug discovery, a lack of common methods for the routine synthesis remains a major obstacle. We have developed a new method for automated glycan synthesis that employs the enzymatic approach and a dendrimer as an ideal support within the chemical process. Recovery tests using a hollow fiber ultrafiltration module have revealed that monodisperse G6 (MW = 58 kDa) and G7 (MW = 116 kDa) poly(amidoamine) dendrimers exhibit a similar profile to BSA (MW = 66 kDa). Characteristics of the globular protein-like G7 dendrimer with high solubility and low viscosity in water greatly enhanced throughput and efficiency in automated synthesis while random polyacrylamide-based supports entail significant loss during the repetitive reaction/separation step. The present protocol allowed for the fully automated enzymatic synthesis of sialyl Lewis X tetrasaccharide derivatives over a period of 4 days in 16% overall yield from a simple N-acetyl-d-glucosamine linked to an aminooxy-functionalized G7 dendrimer.