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.
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.
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.
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.
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.
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.
The following is a detailed workflow for our construction of the DNA-encoded modified glycan library:
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.
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.
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.
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.
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 DNA. (Shi, et al., 2021)
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
for more details if you are interested in our DNA-encoded modified glycan library construction service!Reference
Our mission is to provide comprehensive solutions for glycan research, from library design and high-throughput screening to detailed data analysis and validation.