Cell-based DNA-encoded glycan library (DEGL) screening is a technique that combines the principles of DNA-encoded libraries (DELs) with the screening of glycan structures directly on cell surfaces. The purpose of this method is to identify ligands or small molecules that interact specifically with glycan structures presented on cell membranes, which are often involved in critical biological processes and disease states.
At CD BioGlyco, our cell-based DEGL screening service offers an approach to identifying glycan-protein interactions directly on living cells. In this service, a diverse library of glycan structures, each uniquely encoded with a DNA sequence, is introduced to living cells that express various glycan-binding proteins or receptors on their surfaces. The interactions between the glycans in the library and the cell surface proteins are then captured and analyzed. The DNA tags linked to the bound glycans are recovered, amplified, and sequenced, enabling precise identification of the glycan structures that interact with the target proteins on the cell surface. This method is particularly advantageous because it enables the exploration of glycan-protein interactions within a biologically relevant environment, where proteins maintain their native conformations and are naturally associated with the cell membrane. The detailed workflow of cell-based DEGL screening service follows a meticulous process designed to identify glycan-protein interactions on the surface of living cells, ensuring a biologically relevant context for discovering active ligands.
This library is designed to cover a broad range of potential glycan-protein interactions.
The glycan library is introduced to living cells that express glycan-binding proteins or receptors on their surfaces.
The cells are incubated with the glycan library under controlled conditions to allow specific binding interactions between the glycans and cell surface proteins. After incubation, the cells undergo a series of washes to remove unbound or non-specifically bound glycans.
The bound glycans are then eluted from the cell surface, typically through heating or chemical disruption, which allows the recovery of the DNA-tagged glycan structures that successfully interact with the target proteins.
The recovered DNA tags are amplified using PCR and then subjected to next-generation sequencing (NGS).
The sequencing data is analyzed using advanced computational tools, often incorporating machine learning algorithms, to filter out noise and identify true positive interactions.
The most promising glycan structures are selected for further validation in additional biological assays to confirm their activity and specificity.
Technology: Fluorescence labeling, Live-cell assays, Competitive inhibition, G protein-coupled receptor (GPCR) Targeting
Journal: Biophysics Reports
Published: 2021
Results: The research focuses on the development and application of a cell-based drug screening method that utilizes DEGL to identify responsive cell populations. The method involves individually labeling different cell populations before combining them into a single reaction vessel. After adding the compound to be tested, responsive cells are identified based on their specific labels. The image further illustrates the role of GPCR in the screening process (part B), which is a common target in drug discovery due to its involvement in cellular signaling pathways. Part C of the image shows a competitive inhibition assay where live cells are pre-treated with inhibitor candidates. Potent compounds inhibit the interaction between Hsp90 (a heat shock protein) and its target, which is detected through fluorescence labeling. This method allows for precise identification of active compounds in a physiologically relevant environment, demonstrating the effectiveness of cell-based DEGL screening services in drug discovery.
Fig.1 Scope of application for cell-based assay. (A) Unknown targets can use the whole cells for screening. (B) GPCRs as a target that is difficult for purification. (C) Cell-based ligand-screening system for inhibitor or allosteric inhibitor. (Wei, et al., 2021)
At CD BioGlyco, our cell-based DEGL screening service is an innovative platform designed to identify glycan-protein interactions with high specificity and relevance. Whether you're in drug discovery, functional glycomics, or biomarker research, our service ensures precise and efficient identification of potential therapeutic targets, driving forward the future of glycan-related research. Please feel free to
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Our mission is to provide comprehensive solutions for glycan research, from library design and high-throughput screening to detailed data analysis and validation.