School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
Nat Commun. 2021 Mar 2;12(1):1395. doi: 10.1038/s41467-021-21538-0.
On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously. However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results. In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner. On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface. Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
芯片上的糖基化生物合成是一种有效策略,可用于制备有用的复杂糖源,并同时制备糖参与的应用。然而,当前的方法在分析生物合成的聚糖和优化酶反应时存在一些局限性,这可能导致表面上定义不明确的聚糖结构,从而导致结果不一致和不可靠。在这项工作中,通过引入 pH 响应的 i-motif DNA 接头来开发糖芯片,以 pH 依赖的方式控制糖在芯片表面上的固定和分离。通过逐步定量分析从表面分离的产物,优化了芯片上的酶糖基化反应,以均匀生物合成与癌症相关的 Globo H 六糖及其相关的复杂聚糖。成功地分析了抗 Globo H 抗体与 MCF-7 乳腺癌细胞与芯片上生物合成的 Globo H 相关聚糖的相互作用,证明了基于结构可切换 DNA 接头的糖芯片平台用于芯片上复杂糖基化生物合成和糖参与应用的可行性。