DNA-encoded Modified Glycan Library

DNA-encoded Modified Glycan Library

Overview of DNA-encoded Modified Glycan Library

The cornerstone of our DNA-encoded Glycan Library (DEGL) construction is rooted in our expertise in generating highly diverse and structurally complex glycan libraries. Each cycle of our synthesis process is meticulously designed to introduce variations that contribute to the comprehensive nature of the library.

At CD BioGlyco, we take immense pride in our DNA-encoded modified glycan library construction capabilities. This innovative approach allows us to cater to the diverse and specific needs of our clients, providing bespoke compound libraries that range from millions to tens of millions in terms of complexity and variety.

Leading the New Era of Glycobiology: DNA-encoded Modified Glycan Library Construction

Our synthesis begins with a carefully designed set of starting glycan compounds with diverse chemical structures and potential biological activities. We then assign a unique DNA tag to each starting glycan molecule to ensure its traceability in subsequent steps.

Initial Functionalization

Reaction: Glycosylation initiation.

Process: Initially, a core scaffold is functionalized using a glycosyltransferase reaction, introducing the first glycan monomer to the scaffold.

Product: A basic glycan unit embedded within a DNA sequence encoding its structure. This forms the foundation upon which further complexity can be built.

Cycle 1: Branch Extension

Reaction: Glycosylation extension.

Process: Through chemical glycosylation, additional glycan monomers are added to the core scaffold.

Product: A progressively complex glycan structure with an extended chain or branching pattern, each step uniquely encoded within the DNA sequence.

Cycle 2: Diversification

Reaction: Glycan modification.

Process: Various modifications, such as sulfation, phosphorylation, or acetylation, are introduced.

Product: Diversified glycan molecules exhibiting functional groups that enhance biochemical interactions, encoded appropriately within the DNA framework.

Saturation and Completion

Reaction: Reductive amination or oxidative coupling.

Process: Final touches are added to the glycan scaffold, ensuring maximal diversity and reactivity.

Product: Fully functional DEGL. These libraries span from relatively small collections to vast, highly diverse libraries of several million distinct glycan configurations.

The above steps are repeated continuously, and through multiple iterations of synthesis cycles, we gradually build a DNA-encoded modified glycan library with complex structure and rich diversity. Each cycle introduces new glycan units or structural variations, thereby increasing the molecular diversity and biological activity potential in the library.

DNA-encoded modified glycan library construction cycles. (CD BioGlyco)

Workflow

The following is a detailed workflow for our construction of the DNA-encoded modified glycan library:

Project Planning and Preparation

We conduct project planning to clearly define the goals, expected scale, and resources required for building a DNA-encoded modified glycan library. This includes determining the types of glycans, the selection of modifying groups, the design of DNA tags, and the synthesis strategy.

Selection and Synthesis of Building Blocks

Based on rich chemical libraries and bioinformatics analysis, we carefully select high-quality glycan building blocks. These building blocks have diverse chemical structures and potential biological activities. Subsequently, we prepare these molecular building blocks through chemical synthesis methods and ensure their purity and structural correctness.

Synthesis of DNA-Encoded Modified Glycans

We connect molecular building blocks with corresponding DNA tags that are attached to the DNA starting molecular before through specific chemical reactions to form DNA-encoded modified glycans. Upon completion of the reaction, these on-DNA glycans are mixed, and the 1-cycle compound library is purified and re-dissolved. It is then evenly divided and subjected to the same process for the selected on-DNA conjugation reaction to form a 2-cycle DEGL.

Library Screening and Identification

The constructed DNA-encoded modified glycan library is incubated with a specific target, and the affinity binding force between small molecules and proteins is used to screen out molecules with potential biological activity.

Applications of DNA-encoded Modified Glycan Library

  • Accelerating glycobiology research: DNA-encoded modified glycan library provides an efficient tool for glycobiology researchers, enabling them to systematically explore the interaction between different glycan molecules and other biomolecules.
  • Drug target found: DNA-encoded modified glycan library helps researchers to quickly identify and verify these potential drug binding sites to provide clues to develop new targeted drugs.
  • Bio-material design and optimization: DNA-encoded modified glycan library can be used to design and optimize the surface characteristics of biomass materials, and enhance the ability of the cells to adhere, grow, and differentiate the cells.

Advantages

  • Order-level compound libraries: Whether you require a modest library in the millions or an extensive collection in the tens of millions, we do our best to meet your requirements.
  • Client-centric solutions: Our technical team works closely with clients to understand their specific needs, ensuring that each glycan library is tailored to meet precise research objectives.
  • Cutting-edge technologies: Leveraging the latest developments in synthesis, purification, and characterization techniques, we ensure high-quality products with exceptional reproducibility.

Publication

Journal: RSC advances

IF: 3.9

Published: 2021

Results: The authors summarized a series of novel DNA-compatible chemistry reactions used for DEL building blocks. They noted that the application of DEL technology offered significant advantages during the initial stages of drug discovery, particularly in terms of reducing cost, time, and storage space for identifying target compounds. The authors identified key aspects for constructing DELs, which included developing and selecting encoding methods, adapting routine chemical reactions from off-DNA to on-DNA, and exploring new chemical reactions that occur on DNA. Through the use of novel DNA-compatible reactions involving the formation and cleavage of various bonds, the limitations in the chemical space and diversity of DEL were gradually reduced.

Fig.1 Redox and acylation reactions on deoxyribonucleic acid.Fig.1 Redox and acylation reactions on DNA. (Shi, et al., 2021)

Frequently Asked Questions

  • How does your company ensure the quality and diversity of DNA-encoded modified glycan libraries?
    • Our company has adopted a series of strict quality control measures and innovative synthesis strategies to ensure the quality and diversity of DNA-encoded modified glycan libraries. First, we carefully select the initial glycan units and select diverse DNA tags to ensure that each glycan molecule can be accurately tracked. Secondly, during the synthesis process, we use efficient glycosyltransferases and advanced chemical synthesis methods to ensure the high yield and purity of each step of the reaction. In addition, we regularly perform structural characterization and use advanced technologies such as MS to characterize the product. Finally, we continuously introduce new glycan units and structural variations through a cyclic iteration method to construct a glycan chain library with wide coverage and high diversity.
  • Can your company provide a customized DNA-encoded modified glycan library?
    • Yes, our company provides a customized DNA-encoded modified glycan library. We have a professional R&D team and advanced synthesis technology platform to design and construct glycan libraries with specific structures and properties according to the specific needs of clients. Whether it is drug screening for specific disease targets or functional analysis of glycan chains for basic scientific research, we provide personalized solutions. During the customization process, we work closely with clients to provide technical support and consulting services throughout the project cycle.

At CD BioGlyco, our DNA-encoded modified glycan library construction process is a testament to our commitment to innovation and customization. Our methodically structured synthesis cycles and advanced capabilities empower us to provide clients with highly detailed and functionally diverse glycan libraries, driving forward the frontiers of glycomics research. Please feel free to contact us for more details if you are interested in our DNA-encoded modified glycan library construction service!

Reference

  1. Shi, Y.; et al. DNA-encoded libraries (DELs): a review of on-DNA chemistries and their output. RSC advances. 2021, 11(4): 2359-2376.
For research use only. Not intended for any clinical use.
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