DNA-encoded Glycan Covalent Inhibitor Library
Overview of DNA-encoded Glycan Covalent Inhibitor Library
DNA-encoded library (DEL) technology is one of the screening tools for small molecule compounds, which plays an important role in the field of drug discovery and development due to the advantages of short time-consuming synthesis and screening process, and high throughput. A glycan covalent inhibitor is an inhibitor that exerts its biological function by irreversibly binding to the target through covalent bonds. In recent years, glycan covalent inhibitors have shown significant advantages in the field of drug development.
At CD BioGlyco, we combine DEL technology with a variety of glycan covalent inhibitors or glycan small molecule compounds with covalent reactive groups to construct a novel and structurally diverse DNA-encoded glycan covalent inhibitor library, which can help our clients conduct covalent inhibitor screening research.
Unlocking Innovations with DNA-encoded Glycan Covalent Inhibitor Library
Our professional DNA-encoded Glycan Library (DEGL) research team discusses the applicable glycans and target proteins with clients based on their needs and research objectives. Through in-depth analysis of the target, we design the appropriate DNA coding strategy and glycan structure, synthesize the appropriate DNA coding fragments, and then construct a DNA-encoded glycan covalent inhibitor library to meet the client's needs.
Preparation of DNA Coding Fragments
We prepare different DNA sequences for each glycan covalent inhibitor or glycan small molecule compound with a covalent reactive moiety as its coding tag. Specific steps include:
- Sequence design. Bioinformatics tools are used to identify the most suitable coding sequence to ensure that each glycan covalent inhibitor or glycan small molecule compound with a covalent reactive moiety has a unique identifier.
- Synthesis and purification. Coding sequences are synthesized using efficient DNA synthesis techniques and purified to ensure high-quality DNA fragments.
- Verification. The synthesized DNA fragments are verified by sequencing and other means to ensure their correctness.
Construction of DNA-encoded Glycan Covalent Inhibitor Library
Each DNA coding fragment is coupled to a corresponding glycan covalent inhibitor or a glycan small molecule compound. After that, a DNA-compatible chemical reaction connecting the DNA fragment with the glycan covalent inhibitor should be selected. Reactions include amide bond construction, on/off Boc protection reactions, ester group hydrolysis, and Suzuki-Miyaura coupling reactions. Of course, we also provide custom DNA-Compatible Reactions according to the client's research needs.
We apply the constructed DNA-encoded glycan covalent inhibitor library to target biological systems, such as specific enzymes, proteins, or cells, for screening of glycan covalent inhibitors. In this process, we use appropriate screening methods, such as affinity capture screening, to identify and screen small molecule compounds that meet our clients' needs.
In addition, we also provide DNA sequencing analysis of the screened active molecules to help clients analyze the structure-activity relationship of glycan covalent inhibitors.
According to the needs and applications of our clients, we not only provide various kinds of custom DNA-encoded glycan covalent inhibitor libraries but also provide different packaging methods, such as solution packaging and powder packaging, for all products in the library, to ensure that we help our clients to complete the relevant research efficiently.
Workflow
Through our expertise in DNA coding technology and innovative chemical biology methods, we provide you with a comprehensive solution for the DNA-encoded glycan covalent inhibitor library from Library Design to efficient screening. Below is our detailed workflow diagram, which will take you through the precise operation and key aspects of each step, helping you make breakthroughs in your research.
Applications
- Drug discovery. The DNA-encoded glycan covalent inhibitor library enables rapid screening of a large number of highly active and selective glycan covalent inhibitors, which can significantly accelerate the drug discovery process.
- Biomarker discovery. The DNA-encoded glycan covalent inhibitor library can be used to discover new biomarkers that can be used in research for prognostic assessment.
- Target validation. The DNA-encoded glycan covalent inhibitor library enables rapid screening of a large number of different glycan inhibitors, which can be used to research the role of new or known molecular targets in disease.
Advantages
- Customized design. We customize the design and construction of various kinds of DNA-encoded glycan covalent inhibitor libraries according to client's needs to ensure that they meet their scientific requirements.
- High-throughput screening. We provide high-throughput screening services to help clients quickly identify potential high-efficiency glycan inhibitors using DNA-encoded glycan covalent inhibitor libraries.
- Follow-up support. After the construction of the DNA-encoded glycan covalent inhibitor library is completed, we also provide follow-up data analysis and optimization services to ensure that the client's research and applications are carried out efficiently.
Publication Data
Technology: DEL
Journal: ACS Infectious Diseases
IF: 4.0
Published: 2024
Results: In this article, the authors describe the application of DEL in the screening of the inhibitor polyketide synthase 13 (Pks13). In the DEL screen for Pks13, the authors identified five different novel inhibitor series, three of which had IC50 values in the nanomolar range and structure-activity relationship (SAR) potency. The authors also employed X-ray crystallography to verify that all series of compounds bind deep within the active site of Pks13, thus uncovering potential new contact information and additional active site conformations for virtual screening and drug design efforts. In addition, the authors found that DEL screening yielded a larger amount of data compared to traditional high-throughput screening results, which could also be a good training set for artificial intelligence (AI)-based discovery of new leads.
Fig.1 Enrichment data for building block combinations in each of the DELs from which series 1, 2, and 3 were sourced. (Krieger, et al., 2024)
Frequently Asked Questions
- What is the process of DEGL screening?
- The basic process of DEGL screening is that after incubating DEGL with the target, based on the affinity binding force of glycan small molecules-proteins, non-binding glycan small molecules are removed by different elution methods to achieve high enrichment of glycan small molecule ligands with high affinity. Then, by combining PCR amplification and next-generation sequencing, the compound information can be decoded according to the DNA tags of the glycan molecules.
- What molecules can DEL screen?
- DEL is a powerful tool for screening large-scale molecular libraries for potential drugs or functional molecules. Examples include small molecule drugs, protein-protein interaction inhibitors, chemical probes, natural product analogs, peptides and their modifiers, nucleic acid drugs, sugar derivatives, and more. Overall, DEL can be used to screen a variety of types of molecules that have validated and diverse applications, including but not limited to the fields of drug discovery, basic biological research, and therapeutic performance evaluation.
CD BioGlyco has a dedicated DEGL research team to provide custom solutions for DNA-encoded glycan covalent inhibitor libraries to clients in different fields. The design and construction of our DNA-encoded glycan covalent inhibitor library adopts the latest molecular biology and chemistry techniques, which can provide efficient and accurate screening of target molecules. Please feel free to contact us for more information about DEGL.
Reference
- Krieger, I.V.; et al. Inhibitors of the thioesterase activity of Mycobacterium tuberculosis Pks13 discovered using DNA-encoded chemical library screening. ACS Infectious Diseases. 2024, 10(5): 1561-1575.
For research use only. Not intended for any clinical use.
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