Overview of DEDL

Dynamic combinatorial libraries (DCL) are based on the principles of dynamic combinatorial chemistry and have become an effective tool for the discovery of novel ligands against biological targets. DNA-encoded Glycan Libraries (DEGLs) are a combinatorial library approach that uses a mixture of compounds in library processing, where each compound is linked to a unique DNA tag. Due to the high coding capacity of DNA, DEGL contains millions of different compounds and easily decodes library selections using polymerase chain reaction (PCR) amplification and DNA sequencing.

At CD BioGlyco, we use cutting-edge DEL and combinatorial chemistry technologies to introduce DNA-encoded glycan fragments into DCLs and construct personalized DEDL based on the principles of fragment-based drug discovery.

Beyond Limits with DEDL

The construction of DEDL often involves a series of delicate steps to ensure that each glycan molecule corresponds to a unique DNA sequence, facilitating subsequent screening and analysis.

Construction of Libraries

Glycan-DNA linkage construction is mainly divided into the steps of glycan preparation, DNA sequence preparation, and glycan-DNA assembly.

• According to the client's requirements, our team selects glycans that can be chemically interconverted (dynamic combinatorial conversion) as the basis for subsequent library construction. In dynamic libraries, glycans can be dynamically transformed in the following ways:
  • Ligand exchange reactions. Ligands are continuously exchanged in a reaction pool to mimic in vivo conditions.
  • Chemical modification. We use different enzymes or chemical reactions to modify the structure of the glycan moiety.
  • Light-controlled/thermal-controlled dynamic transformations. We use changes in the external environment (e.g. light and temperature) to direct the dynamic transformation of molecules.
• We prepare different DNA sequences to bind with specific glycan molecules, thus each compound contains unique coding sequences.
• Appropriate chemical reactions (e.g. click chemistry, amide bond construction, ester hydrolysis, Suzuki-Miyaura coupling, etc.) are used to efficiently and quantitatively bind the glycan molecule to the DNA sequence to be encoded. In other words, each DNA sequence identifies a unique glycan molecule, thus "coding" it.
  • Afterward, we purify the DEGL using appropriate purification methods to ensure high purity. The composition and structure of the glycan-DNA conjugates are verified using mass spectrometry and other analytical tools.

All DNA-encoded glycans are combined to obtain a DEDL. The library achieves constant conversion between components by a dynamic equilibrium mechanism, e.g., adding protein targets to the library triggers selective pressure, which alters the library's equilibrium. At the same time, we also use kinetic regulation, i.e., adjusting conditions (e.g., pH, temperature, catalysts, etc.) to affect the dynamic conversion rate and equilibrium between glycan molecules in the library, to ensure the diversity and dynamics of the library content, and to achieve continuous conversion and equilibrium adjustment of the library components.

We also provide methods such as quantitative PCR to measure the concentration and diversity of libraries to ensure that the libraries obtained meet clients' research needs.

Screening and Use of the Library

We provide DEDL for High-throughput Screening (HTS) of many types of molecules, including but not limited to glycoproteins, protein inhibitors, enzymes, and antibodies.

Furthermore, we dynamically adjust and resynthesize new DNA fragments based on the screening results, so that the DEDL is continuously optimized and its functionality is enhanced.

Workflow

By combining DEL technology with dynamic combinatorial chemistry, we efficiently generate personalized DEDL. The following is a detailed description of our service process, to help you quickly understand the key aspects included in each step and their benefits.

Applications

• DEDL can be used to efficiently screen and characterize the interactions of glycan molecules with specific proteins (e.g., glycan recognition receptors, antibodies, etc.). This contributes to the understanding of the mechanism of action of glycoproteins and glycolipids in biological processes.
• Researchers can use DEDL to identify and optimize glycosylated drug molecules, thereby accelerating the development of antibodies, vaccines, and other glycan-based drugs.
• Glycoantigens play an important role in vaccine development. The use of DEDL allows for the rapid screening of high-quality glycoantigens against specific pathogens, aiding in the development of highly effective vaccines.

Advantages

• We bring together experts in the fields of molecular biology, chemistry, and glycobiology to provide our clients with a diversity of DEDLs to meet their multiple needs in glycan molecular research.
• With advanced HTS technology, we rapidly screen target molecules from large-scale DEDLs, improving our clients' R&D efficiency and accelerating scientific discovery.
• According to the specific needs of our clients, we provide comprehensive customized services, including DEDL design, synthesis, screening, analysis, etc., to ensure that the products and services delivered are fully in line with our clients' research directions and objectives.

Publication Data

Frequently Asked Questions

• What is the difference between traditional HTS and HTS in DEL technology?
  • Traditional HTS and DEL are two technologies used for drug discovery, but they have significant differences. HTS focuses on screening large numbers of compounds directly through automated laboratory equipment. However, DEL encodes chemical information before screening through innovative DNA-encoding methods, improving screening efficiency and enabling the handling of larger compound libraries.
• Is DEDL applicable to all types of targets?
  • DEDL is mainly suitable for those targets that can be immobilized or labeled, such as proteins or cell surface receptors. Special methods may be required for specific, difficult-to-labeled targets.

CD BioGlyco has a wealth of experience and expertise in the construction and application of DEDL. We provide comprehensive solutions from DEDL design, synthesis, and screening to data analysis, ensuring efficient and reliable research results for our clients. In addition, our DEDL platform features automation, high throughput, and high sensitivity, which greatly improves screening efficiency and accuracy of results. Please feel free to contact us if you would like to learn more about the DEDL field.

• DNA-encoded Single-Pharmacophore Glycan Library
• DNA-encoded Dual-Pharmacophore Glycan Library
• DNA-encoded Trio-Pharmacophore Glycan Library
• Solid Phase-based DNA-encoded Glycan Library (DEGL)
• Liquid Phase-based DNA-encoded Glycan Library (DEGL)
• DNA-encoded Natural Glycan Library
• DNA-encoded Modified Glycan Library
• DNA-encoded Glycan Antigen Library
• DNA-encoded Glycopeptide Library
• Monovalent DNA-encoded Glycan Library (DEGL)
• Multivalent DNA-encoded Glycan Library (DEGL)
• Scaffold-based DNA-encoded Glycan Library (DEGL)
• Target-based DNA-encoded Glycan Library (DEGL)
• DNA-encoded Glycan Macrocycle Library
• DNA-encoded Glycan Covalent Inhibitor Library
• DNA-encoded Glycoprotein Degrader Library
• DNA-encoded Glycan Allosteric Inhibitor Library
• Light Crosslinking DNA-encoded Glycan Library (DEGL)
• Coupling Reaction-based DNA-encoded Glycan Library (DEGL)
• Multi-component Reaction-based DNA-encoded Glycan Library (DEGL)
• Photocatalytic Cycloaddition-based DNA-encoded Glycan Library (DEGL)
• Aromatic Heterocyclization-based DNA-encoded Glycan Library (DEGL)
• Non-aromatic Heterocyclization-based DNA-encoded Glycan Library (DEGL)
• Carbocyclization-based DNA-encoded Glycan Library (DEGL)
• Macrocyclization-based DNA-encoded Glycan Library (DEGL)
• Click Chemistry-based DNA-encoded Glycan Library (DEGL)