Monovalent DNA-encoded Glycan Library (DEGL)

Monovalent DNA-encoded Glycan Library (DEGL)

Overview of Monovalent DEGL

CD BioGlyco is at the forefront of DEGL and is dedicated to facilitating groundbreaking research in glycobiology and drug discovery. Monovalent DEGL is one of our flagship services, and it is designed to provide researchers with unparalleled access to highly diverse glycan structures. Glycans play crucial roles in numerous biological processes, making them vital for the development of therapeutic agents and diagnostics. Our DEGL service is tailored to meet the bespoke needs of our clients, enabling the synthesis, customization, and screening of glycan libraries on a scale previously unattainable.

Explore Infinite Possibilities in Immunology with Monovalent DEGL

The construction of monovalent DEGL is a comprehensive project integrating chemical synthesis and molecular biology. Its core is to connect the glycan molecules to a unique DNA sequence to form a glycan-DNA conjugate, thereby achieving accurate encoding and rapid screening of the glycan structure. This monovalent connection method ensures the independence and activity of the glycan molecules in subsequent experiments and avoids non-specific interactions that may be caused by multivalent connections.

Schematic diagram of the construction process of monovalent DEGL. (CD BioGlyco)

Glycan Synthesis and Activation

We use advanced techniques to gradually construct the target glycan structure. During the synthesis process, the reaction conditions are strictly controlled to ensure the correctness and purity of the glycan structure. Subsequently, the glycan molecules are made active to connect to DNA biological method.

Library Construction

In each construction cycle, we covalently link the activated glycan molecules to the DNA template. This step usually involves click chemistry, amidation reaction, or other selective connection strategies. A stable conjugate is formed between the glycan and the DNA by precisely controlling the reaction conditions while maintaining the biological activity of the glycan and the coding information of the DNA. In each cycle, new glycan structural units are introduced or structurally modified, and they are integrated into the library through the above-mentioned DNA encoding and ligation reactions. DEGLs with diverse structures and large scales are gradually constructed through multiple cycles of operation.

Purification and Identification

After the library is constructed, the unreacted raw materials and by-products are removed by purification techniques to obtain a high-purity glycan-DNA conjugate library. Subsequently, the library is identified and characterized by means of time-of-flight mass spectrometry (TOF-MS) to confirm the reaction completed.

Workflow

Design

  • Client consultation: We begin with an in-depth consultation to understand the scientific goals and specific requirements of our clients.
  • DEGL design: Our team of experts collaborates with clients to select the glycan structure, the corresponding DNA tags, and the DNA-compatible reactions used in the DEGL construction.

Synthesis

  • Monomer preparation: The appropriate monosaccharides are prepared and protected for iterative glycosylation.
  • Iterative glycosylation cycles: Employing our proprietary automation technology, glycosylation cycles are conducted with rigorous monitoring to ensure precise glycan assembly.
  • DNA tagging: Glycans are then conjugated with their different DNA tags to generate the final DEGL.

Quality Control and Validation

Advanced analytical techniques such as mass spectrometry are utilized to confirm the quality of DEGL.

Library Delivery and Support

  • Library packaging: The finalized DEGL is carefully packaged and delivered to the client.
  • Post-delivery support: We provide comprehensive support, including protocols for glycan screening, data analysis, and interpretation to maximize the utility of the glycan library in ongoing research programs.

Applications of Monovalent DEGL

  • Basic research in glycobiology: DEGL provides a powerful tool for studying the interaction between glycans and glycan-binding proteins.
  • New drug discovery and candidate drug optimization: The application of DEGL accelerates the discovery process of lead compounds.
  • Disease mechanism research: Through DEGL technology, researchers systematically analyze the changes in the interaction between glycans and proteins in disease states and reveal the molecular mechanisms of disease occurrence and development.

Advantages

  • Our monovalent DEGL enables high-throughput screening with unparalleled precision, allowing us to swiftly identify key glycan interactions.
  • Our DEGL construction significantly enhances the specificity of molecular recognition, thus ensuring that we focus on the most promising candidates for further exploration.
  • By employing the DEGL platform, we develop personalized glycan-based strategies, ensuring that our innovations remain at the forefront of cutting-edge biotechnological advancements.

Publication

Technology: A technique for preparing and selecting DNA-encoded dynamic libraries (DEDLs)

Journal: Chemical Science

IF: 7.6

Published: 2015

Results: The authors detailed a technique for preparing and selecting DEDLs. Their library consisted of two sets of DNA-linked small molecules that dynamically exchanged through DNA hybridization. When a protein target was added, the equilibrium shifted to favor the formation of high-affinity bivalent binders. Significantly, the authors incorporated an innovative locking mechanism to halt the dynamic exchange, effectively "freezing" the equilibrium. This allowed for downstream hit isolation and subsequent decoding through PCR amplification and DNA sequencing. Their DEDL method overcame the constraints of library size, enabling the evaluation and selection of large dynamic libraries. Furthermore, this approach did not require modified or immobilized target proteins.

Fig.1 Schematic diagram of DNA-encoded dynamic library construction.Fig.1 Schematic diagram of DEDL construction. (Li, et al., 2015)

Frequently Asked Questions

  • What is DEGL and why is it important?
    • DEGL is a high-throughput and diverse glycan molecule library constructed using DNA encoding technology. Each glycan molecule is labeled with a unique DNA sequence, which enables the simultaneous evaluation of the interaction of a large number of glycans with glycan-binding proteins or other biomolecules. Its importance lies in that it greatly accelerates the research process in the fields of glycobiology, drug discovery, and biomaterial development, and provides a powerful tool for revealing the mechanism of glycoside-glycan binding protein interaction and discovering new bioactive molecules.
  • How to use DEGL for high-throughput screening?
    • High-throughput screening using DEGL usually involves the following steps:
    • DEGL is mixed with the target glycan-binding protein or other biomolecules.
    • The glycan-DNA complexes bound to the target molecule are isolated using specific screening methods (such as affinity chromatography and flow cytometry).
    • The DNA sequences of these complexes are analyzed by sequencing technology to determine the glycan molecules bound to them.
    The whole process achieves rapid and accurate screening of a large number of glycan molecules.

At CD BioGlyco, our monovalent DEGL construction technology is a highly specialized, comprehensive, and customized service. We provide clients with high-quality glycan libraries with advanced chemical synthesis technology, precise DNA encoding and ligation strategies, and strong customized synthesis capabilities. These libraries help clients achieve breakthrough progress in the fields of glycoprotein interactions, disease mechanisms, and drug development. Please feel free to contact us for more details if you are interested in our monovalent DEGL construction service!

Reference

  1. Li, G.; et al. Design, preparation, and selection of DNA-encoded dynamic libraries. Chemical Science. 2015, 6(12): 7097-7104.
For research use only. Not intended for any clinical use.
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