Overview of DNA-encoded Library (DEL)-based Inhibitor Discovery

The design and screening of DNA-encoded glycan library (DEGL) plays a key role in the screening of inhibitors. For example, the discovery of inhibitors of RIPK1 and sEH was made possible by the rapid availability of a large number of compounds through DEL screening, and DELs can be constructed to target a specific chemical space to find tool compounds rather than just drug-like compounds. Library design is also very important in this, and the fact that the final candidate compounds are very similar to the initial ligands found in the DEL screen highlights the importance of library design. Compounds with potential drug-like properties can be obtained by designing DEL libraries and screening them and can be developed into clinical candidates through further optimization and development.

Fig.1 The chemical structures of the targeting RIPK1 (A) and sEH (B) from first discoveries from DEL screenings to the potential drugs after medicinal chemistry optimizations. (Ottl, et al., 2019)

Unlocking the Secrets of Glycans with Our DEGL Design

The advent of DEL has revolutionized the field of chemical biology, enabling the High-throughput Screening of vast chemical space with unprecedented precision. Among these, DEGLs have emerged as a powerful tool for exploring carbohydrate biology, glycobiology, and glycomics. DEGLs integrate the specificity of glycan interactions with the versatility of DNA encoding, providing a robust platform for identifying glycan-binding proteins, elucidating carbohydrate-protein interactions, and discovering new glycan-based therapeutics. CD BioGlyco has a specialized platform to provide comprehensive DEGL design services from chemical, biological, and artificial intelligence (AI)-assisted perspectives.

Workflow

We begin by thoroughly discussing the research objectives and requirements with the client. We then analyze the three-dimensional structural information of the target to identify potential binding sites and key interaction regions. After that, we select suitable building blocks, taking into account their physicochemical properties (PCPs) and structural diversity. Our experts assess whether the chosen chemistry and synthetic protocols are compatible with DNA barcoding, and develop specific synthetic routes in conjunction with known DNA-compatible chemistry and synthetic protocols. Using computer-aided drug design software, we design DEGLs containing building blocks of specific functional groups and conduct virtual screening to simulate compound-target interactions and binding affinities. Finally, AI tools are used to efficiently screen potentially active glycan molecules, reducing experimental time and resource consumption. The most promising candidate molecules are prioritized for experiments based on predicted biological activities and functions.

Applications

• DEGL can be used for the discovery of novel drugs and is of great importance for deepening our understanding and use of glycobiochemistry.
• By using DEGL, researchers can rapidly and efficiently screen and identify biologically active glycoconjugates, which can facilitate drug discovery, biomarker discovery, and even personalized glycobiology.
• DEGL can be used to help researchers design and optimize glycoconjugates as vaccine candidates or immunomodulators for enhancing the immune system's ability to respond to diseases.

Advantages

• We custom-design DEGLs according to your experimental needs and target studies, with the flexibility to adjust the type and number of glycosyl structures.
• Our DEGL design can provide a wealth of information, including information on the structure, properties, activity, and affinity of each compound. These data help to better understand the relationships between glycoconjugates and guide subsequent analysis and optimization.
• Our DEGL designs can contain hundreds to thousands of glycoconjugates with a wider range of chemical structures and diversity.

Publication Data

Frequently Asked Questions

• What is the construction principle of DEGL?
  • The construction principle of DEGL is to link sugar molecules to DNA sequences to form a coding library containing different sugar compounds. Each sugar-nucleotide corresponds to a unique code. By screening and analyzing the DNA sequences, the structure and activity of different sugar molecules can be recognized and identified.
• What are the advantages of DEGL over traditional methods?
  • High-throughput screening: DEGL can process a large number of glycoconjugates in a single experiment, enabling high-throughput screening and speeding up the process of glycoconjugate discovery and identification.
  • Highly controllable: Through the design of DNA sequences, glycoconjugates can be accurately coded and labeled to achieve precise screening and identification.
  • Versatility and ease of use: DEGL has a rich structural diversity, covering a large number of different types of glycoconjugates, and is easy to use for laboratory operation and automated processing.

CD BioGlyco combines advanced chemical synthesis, structural analysis, and AI technologies to design and build highly diverse libraries of glycoconjugates that will unravel complex biological interactions and discover potential drug targets for you! If you are interested in our service, please feel free to contact us!

• DNA-Compatible Reaction Development
• DNA-encoded Glycan Library (DEGL)
• High-throughput Screening (HTS) of DNA-encoded Glycan Library (DEGL)
• Next-generation Sequencing of the High-throughput Screening (HTS) Output
• Data Analysis and Visualization
• Hit Validation and Assessment