Target-based DNA-encoded Glycan Library (DEGL)

Overview of Target-based DNA-encoded Glycan Library (DEGL)

At CD BioGlyco, we specialize in providing cutting-edge and customized solutions for researchers working on drug discovery and glycobiology. DEGL has great potential in the study of glycobiology. Our target-based DEGL service enables the synthesis of highly diverse libraries of carbohydrate compounds directed against specific biological targets. By utilizing state-of-the-art technologies and methodologies, we help our clients identify potential therapeutics with high specificity and efficacy. Our DEGL service meets your specific research needs, providing tailored compound libraries that greatly enhance the drug development process.

Innovative Solutions with Target-based DEGL, Elevating Glycan-target Research for Tomorrow's Medical Breakthroughs

The construction of a target-based DEGL incorporates a sophisticated blend of molecular biology and organic chemistry techniques to generate highly diverse libraries of carbohydrate compounds, encoded uniquely by DNA tags. This approach facilitates the efficient screening of a vast array of glycan structures against a specific target.

Schematic diagram of the construction process of target-based DEGL. (CD BioGlyco)

Library Design

Initial Planning: The design of a target-based DEGL starts with a thorough understanding of the client's biological target of interest. We collaborate closely with clients to understand precise requirements and the nature of the biological target involved.
Custom Design: We employ bioinformatics and chemical informatics tools to design a glycan library that contains a wide array of carbohydrate derivatives. Each glycan is strategically chosen to maximize interaction possibilities with the target protein, enzyme, or cell surface receptor.

Synthesis

The synthesis of the target-based DEGL consists of multiple iterative steps. Each cycle builds upon the previous one, introducing new functional groups and increasing the complexity of the glycans.

Activation and Coupling: Each cycle begins with the activation of a starting glycan nucleotide or a monosaccharide derivative. This is followed by a coupling reaction where the activated carbohydrate is linked to another monosaccharide, oligosaccharide, or other chemical moiety.
DNA Tagging: Post-coupling, the nascent glycan is attached to a unique DNA sequence, thus encoding the structure of the carbohydrate. DNA encoding is performed using advanced enzymatic techniques, ensuring each glycan variant in the library is uniquely identifiable.
Purification and Amplification: The resulting DNA-glycan conjugates are then purified using the precipitation method.

Reactions and Chemistry

Diverse Reaction: We employ a broad spectrum of chemical reactions tailored to the creation of glycan structures, including oxidation, reduction, acylation, and sulfation. This versatility allows the construction of complex libraries incorporating a wide range of structural motifs and functionalities.
Automated and High-Throughput Synthesis: Our state-of-the-art automation platforms enable the efficient creation of libraries containing millions to tens of millions of distinct compounds. The customization potential is extensive, allowing the synthesis of libraries as per clients' specific needs, whether require smaller focused libraries or extensive ones with millions of variants.

Workflow

Demand Analysis: First, we communicate with clients in-depth to clarify the biological targets of interest to clients and the expected library size and diversity.

Library Design: Based on client needs, our expert team designs a customized library synthesis plan to determine the structure of the glycan compounds to be synthesized and their corresponding DNA codes.

Library Synthesis: Using an advanced automated synthesis platform, we begin to build the library gradually. Each synthesis cycle strictly monitors the reaction conditions and product quality to ensure the accuracy and diversity of the library.

Quality Control: At each key step of library synthesis, we perform strict quality control, including structure verification and purity checks to ensure the quality of the library.

Delivery and Screening: After completing the library synthesis, we deliver the library to the client and provide the necessary screening support to help clients quickly identify glycan compounds that interact with specific biological targets.

Applications of Target-based DEGL

Discovery of drug lead compounds: By screening carbohydrate compounds in target-based DEGL, molecules with high affinity for specific biological targets can be found.
Identification of biomarkers: Target-based DEGL helps researchers identify carbohydrate biomarkers associated with specific physiological states or disease processes.
Assistance in the development of carbohydrate vaccines: Target-based DEGL can be used to help researchers quickly screen carbohydrate antigens that induce strong immune responses, providing strong support for the development of carbohydrate vaccines.

Advantages

Highly customized: Our target-based DEGL construction service provides highly customized carbohydrate compound libraries according to client needs.
Advanced DNA encoding technology: We use advanced DNA encoding technology to assign a specific DNA tag to each unique carbohydrate compound. This not only ensures the traceability and identifiability of each compound in the library but also greatly improves the screening efficiency and accuracy.
Professional technical support: We have an experienced technical team that provides clients with a full range of technical support and consulting services. Whether it is problems encountered during library design and synthesis, or confusion in subsequent screening and application, we provide professional and timely answers and help.

Publication

Technology: Efficient and expansive compound screenings using DELs

Journal: Trends in Pharmacological Sciences

IF: 13.9

Published: 2022

Results: The authors discuss the transformative potential of DNA-encoded libraries (DELs) in enhancing high-power screening (HPS) processes, which significantly surpass traditional high-throughput screening (HTS) methods. DELs enable efficient and expansive compound screenings, opening new avenues for drug discovery by targeting complex biological interactions and facilitating the development of novel therapeutic candidates, including proteolysis targeting chimeras (PROTACs). The authors highlight that DEL technologies' ability to generate diverse chemical libraries and their combinatorial power position them as critical tools for advancing personalized medicine and addressing current HTS limitations.

Fig.1 Protein targets used with DELs, HTS versus HPS library sizes, and their differentiating parameters. (Sunkari, et al., 2022)

Frequently Asked Questions

What specific help can the target-based DEGL library provide me?
- The target-based DEGL library helps you to study the interactions between glycans and proteins or other biomolecules in depth, thereby revealing the importance of these interactions in biological processes. In addition, screening the compounds in the library helps you discover glycan molecules with high affinity to specific targets, providing valuable lead compounds for drug development or biological research.
Does your company provide screening services after the library is built?
- Yes, we provide professional screening services after the library is built. We have advanced screening platforms and experienced teams, which efficiently help you identify glycan molecules that interact with specific targets. In addition, we also provide customized screening solutions according to your needs to ensure that you can quickly obtain valuable research results.

At CD BioGlyco, we are committed to advancing research through high-quality and customized target-based DEGL services that push the boundaries of glycobiology and drug discovery. Please feel free to contact us for more details if you are interested in our target-based DEGL construction service!

Reference

Sunkari, Y.K. ; et al. High-power screening (HPS) empowered by DNA-encoded libraries. Trends in Pharmacological Sciences. 2022, 43(1): 4-15.

For research use only. Not intended for any clinical use.