DNA-encoded Glycopeptide Library
Overview of DNA-encoded Glycopeptide Library
DNA-encoded Glycan Library (DEGL) has become a groundbreaking technology, enabling the efficient identification of glycans. Glycopeptide libraries, in particular, combine the functionalities of peptides with glycosylation, which is crucial in many biological processes, including cell signaling and immune responses. At CD BioGlyco, we specialize in constructing highly customized DNA-encoded glycopeptide libraries, tailored to meet the specific needs of our clients. Whether you require a library with millions or tens of millions of unique compounds, our advanced synthesis capabilities cater to your precise requirements.
Unveil the Potential of DNA-encoded Glycopeptide Libraries in Drug Discovery and Biomedical Research
The DNA-encoded glycopeptide library construction technology combines chemical synthesis, molecular biology, and high-throughput screening technology. This technology couples thousands of glycopeptide molecules with their unique DNA tags through an automated synthesis platform to form a huge compound library. This technology platform greatly accelerates the drug discovery process, thereby screening candidate molecules with specific biological activities.
Design and Planning
- Molecular design: We design reasonable molecular skeleton and glycan modification strategies based on the structural diversity and biological activity potential of glycopeptides.
- DNA sequence assignment: We assign a unique DNA barcode to each glycopeptide molecule to ensure accurate tracking and identification in subsequent screening.
Synthesis
- Solid phase peptide synthesis (SPPS): We use Fmoc or Boc strategies to gradually extend the peptide chain on a resin or other solid phase carrier. Each cycle includes steps such as deprotection, coupling, capping, and washing.
- Glycan attachment: We use chemical enzymatic or chemical methods to introduce glycans at specific sites of the peptide chain. This may include glycosylation catalyzed by glycosyltransferases or direct glycosidic bond formation reactions.
- DNA conjugation: DNA sequences are attached to glycopeptide molecules by using T4 DNA ligase.
Cycle Iteration
Iterative synthesis: Repeat the above steps, adding a new amino acid or glycan unit in each cycle to construct a complex and diverse glycopeptide library.
Quality Control and Verification
- Purity and structure verification: We use time-of-flight mass spectrometry (TOF-MS) to verify the purity and structure of the synthetic products.
- DNA barcode integrity checks: We confirm the integrity and specificity of the DNA barcode through PCR amplification according to your needs.
Workflow
Design and Planning
Based on client needs, our team of scientists designs the structural framework of the glycopeptide library, including peptide chain sequence, glycosylation site, glycan type, and length to ensure the diversity and targeting of the library.
Automated Synthesis
First, the corresponding DNA tag is covalently bound to the glycopeptide molecule. On the automated synthesis platform, solid phase peptide synthesis (SPPS) and glycosylation reaction cycles are alternated to gradually build the target polypeptide chain and introduce glycosylation modification at the specified position. Each synthesis cycle includes amino acid coupling, deprotection, and purification to ensure precise control and high yield of each step of the reaction and to form a DNA-glycopeptide conjugate library. The molecular weight of the synthesized compound library is characterized by MS.
Data Analysis and Screening Platform
The constructed glycopeptide library will be connected to our proprietary high-throughput screening platform, using a variety of technical means such as biosensors, cell screening, and biological activity evaluation to quickly identify molecules with potential biological activity.
Applications of DNA-encoded Glycopeptide Library
- Drug discovery and optimization: DNA-encoded glycopeptide library construction technology can accelerate the screening process of drug molecules. Researchers can identify candidate molecules that bind to specific biological targets with high affinity by synthesizing a large number of structurally diverse glycopeptide molecules and encoding and linking them with corresponding DNA sequences.
- Basic biological research: DNA-encoded glycopeptide libraries can be used to help scientists reveal the important role of glycosylation modification in biological processes such as cell communication, developmental regulation, and immune response.
- Biological interaction research: DNA-encoded glycopeptide libraries can be used as a powerful tool for in-depth research on the interaction between glycopeptides and proteins, cells, or other biological molecules.
Advantages
- Scale customization: We construct libraries ranging from millions to tens of millions of distinct compounds. This degree of customization ensures that our clients target a broad spectrum of biological activities or focus on highly specific interactions.
- Diverse reactivity: Our extensive suite of chemical and enzymatic reactions allows for the incorporation of novel glycosylation patterns and peptide modifications, enhancing the functional diversity of the library.
- High efficiency: Using advanced purification techniques, we guarantee highly efficient turnaround times for even the most complex library designs.
Publication
Journal: ChemMedChem
IF: 3.45
Published: 2021
Results: The authors introduced various techniques for constructing DNA-encoded libraries (DELs), a technology used for target-based screening that relies on phenotype-genotype coupling. This approach is related to display technologies like phage and RNA display but utilizes organic preparative chemistry for the combinatorial synthesis of numerous encoded molecules. For identifying bioactive molecules, the encoded libraries were usually selected on tagged recombinant proteins immobilized on a surface. However, alternative selection formats in solution or in cells involving covalent capture of compounds or enzymatic steps have also been demonstrated. Moreover, encoded one-bead/one-compound libraries provided the opportunity to perform functional screens in miniaturized assays.
Fig.1 Encoded library technology. (Kunig, et al., 2021)
Frequently Asked Questions
- How does your company ensure the diversity and quality of DNA-encoded glycopeptide libraries?
- We use highly automated synthesis platforms and optimized chemical strategies to ensure the diversity of glycopeptide libraries. Through carefully designed synthetic routes and diverse molecular units, we generate tens of thousands or even billions of structurally unique glycopeptide molecules. At the same time, we implement strict quality control processes, including intermediate purity testing, final product characterization, and DNA sequence accuracy confirmation, to ensure that the glycopeptide molecule is accurately connected to its corresponding DNA tag and maintains high purity.
- If I have special needs or customized glycopeptide library construction projects, can your company provide support?
- Of course! We are committed to providing clients with a full range of customized services to meet unique scientific research or business needs. Our professional team works closely with you whether you need to design a glycopeptide library for a specific target or want to explore new glycans or connection strategies. We have rich experience and advanced technology platforms to ensure the efficient implementation and successful delivery of customized projects.
At CD BioGlyco, our DNA-encoded glycopeptide library construction service brings revolutionary changes to the fields of life science research and drug discovery with its highly customized, efficient, and high-throughput characteristics. We look forward to working with global partners to jointly explore the mysteries of life and create a new era of drug research and development. Please feel free to contact us for more details if you are interested in our DNA-encoded glycopeptide library construction service!
Reference
- Kunig, V.B.; et al. Scanning protein surfaces with DNA-encoded libraries. ChemMedChem. 2021, 16(7): 1048-1062.
For research use only. Not intended for any clinical use.
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