Customized Glycan Chips for Structure-Switchable DNA-based Diagnosis
[POSTECH-Yeungnam University joint research team develops complex glycan chips using pH-responsive DNA linker]
Glycan chip is gaining attention as a microchip that can quickly analyze glycan-related biological interactions such as diagnosis of diseases like cancer by securing glycan*1 at high density on solid surfaces. Recently, a new platform has been developed that can easily fabricate customizable glycan chips.
A research team led by Professor Hyung Joon Cha and Dr. Hye Ryoung Heo of the Department of Chemical Engineering at POSTECH with Professor Chang Sup Kim of the School of Chemistry and Biochemistry at Yeungnam University have together developed a glycan chip platform using the pH-responsive structure-switchable DNA (i-motif DNA) as a linker. This platform allows the separation of biosynthesized glycans on the surface of the chip, thus optimizing the synthesis of complex glycans, rendering it possible to reproducibly fabricate customized glycan chips according to their applicability.
The glycan chip effectively mimics the glycan on the cell’s surface on its own surface and at this instant, the infectious agent can be diagnosed by analyzing the interaction between the glycan and the various biological substances. Although it is possible to fabricate glycan chips with high structural specificity through enzymatic glycosylation on a solid surface, it has been difficult to clearly identify the complex structure of glycans that are biosynthesized on the surface as the synthesis of complex glycans*2 progress.
The research team used i-motif DNA as a linker, which is an intermediary that connects the chip’s surface to the glycan, noting that i-motif DNA can be separated from the hybridized complementary DNA by modifying its structure under low pH conditions. Applying the principle that i-motif DNA switches its structure depending on the pH conditions, the process for synthesizing complex glycans on the surface was optimized through simultaneous quantitative analyses of the biosynthesized glycans and their reaction conditions after separating glycans from the surface. Using the glycan chips made this way, the glycan biomarker for identification of infectious agents (cancer) were clearly identified, and information on the glycan-binding properties of the cancer-specific labeled antibodies was obtained.
The newly developed glycan chip platform can effectively simulate the cell surface, proving to be highly useful in analysis and application of various glycan-related interactions involved in biological processes. In particular, it is anticipated that these customized glycan chips can be easily fabricated via on-chip biosynthesis through a combination of various glycan-processing enzymes.
“By developing a new glycan chip platform, we solved the issues in synthesizing complex glycans and fabricating glycan chips, and expanded their applicability,” explained Professor Hyung Joon Cha on the significance of the study. He added, “Through this study, fabrication of customized glycan chips will be made more accessible, increasing its utility in various glycan-related studies including cancer diagnosis in the future.”
Published in Nature Communications on March 2, 2021, this study was conducted as part of the Basic Core Technology Development Program for the Oceans and the Polar Regions, and the Basic Science Research Program of the National Research Foundation of Korea.
1. Glycan (carbohydrate)
A biological material that exists in the body as a complex of various forms such as glycolipids and glycoproteins, and plays an important role in various biological interactions such as protein binding and folding, signal transduction, and immunological reactions.
2. Complex glycan
Compound carbohydrates made by linking short, long, or branched monosaccharides of various structures.