Overview of DNA-encoded Glycan Library (DEGL) Screening for Protein-templated Ligand Discovery

The discovery and identification of potent ligands that regulate the function of protein targets is critical for chemical biology and drug discovery. DEGL is a very powerful technology for protein-templated ligand discovery with multiple advantages such as access to a large number of compounds, fast experimental turnaround, and high protein utilization. With advanced platforms, expertise, and technology, CD BioGlyco offers customized DEGL screening solutions for the discovery of protein-templated ligands.

Directing in Situ Ligand Synthesis by DEGL High-throughput Screening

We use the template effect of the target in DEDL selection to guide in situ ligand synthesis. Each compound in DEGL binds to a unique DNA tag. This tag encodes the corresponding chemical structure and serves as an amplifiable label for hit compound decoding by next-generation sequencing (NGS). With multiple selection experiments and in-depth data analysis, our reliable and efficient process has been successful in projects across target types. The process is described below:

Library Design and Construction

We have efficient computational tools to calculate sequence complementarity and design DNA sequences. Experimental parameters for generating DEGLs are also optimize. A large number of compounds with a wide variety of chemical structures and properties are then synthesized, each bound to a unique DNA barcode to maximize the chances of finding the target.

Library Screening

Target proteins are incubated with DEGL libraries. After incubation, the samples are subjected to ethanol precipitation and separation. Target template templates the in situ synthesis of the ligand and only the ligand assembled on the protein is decoded.

NGS

DNA barcodes of retained compounds are amplified using polymerase chain reaction (PCR) to enrich them for further analysis. The amplified products are passed through NGS and analyzed by sequencing.

Data Analysis

We have proprietary bioinformatics tools to convert sequencing data to chemical structures and analyze the resulting ligands for enrichment folds and structural features. Compounds with high enriched folds and high post-selection sequencing counts are considered potential hit compounds.

Hit Validation and Evaluation

The hit compounds are re-synthesized for bioactivity analysis, potency analysis, and other characterization. Concurrent medicinal chemistry efforts are used to optimize compound potency, selectivity, and other properties.

Workflow

Our DEGL screening has been validated in protein-targeted glycans, Protein-protein Interaction Inhibitor development, and more. In consultation with our clients, we develop tailored screening strategies based on the specific research objectives.

Applications

• Drug discovery and development: DEGL screening plays an important role in drug discovery by finding protein-templated ligands to identify target protein ligands associated with various diseases, thus accelerating drug discovery and research on disease therapeutics.
• Protein-protein interaction research: The use of DEGL screening to search for protein-templated ligands helps identify compounds that inhibit or modulate protein-protein interactions, thus promoting protein-protein interaction research.
• Enzyme inhibition research: The use of DEGL screening for protein-templated ligands helps to identify small molecule inhibitors that target the active or metastable sites of enzymes, which is valuable for the development of therapies for a variety of diseases.

Advantages

• We offer a full range of DEGL screening solutions for the discovery of protein-templated ligands, including library synthesis, screening for compounds that bind to target proteins, sequencing, hit validation, and lead optimization through medicinal chemistry.
• With our extensive experience in DEGL High-throughput Screening, the DEGL screening process for the discovery of protein-templated ligands is simpler to design and operate.
• Our DEGLs contain compounds in the millions of equivalents to maximize hit rates.

Publication Data

Frequently Asked Questions

• What are the advantages of DEGL screening in protein-templated ligand discovery?
  • DEGL screening offers several advantages, including the ability to screen large chemical libraries in high throughput, the low amount of protein required, and the potential to discover novel ligands for multiple target proteins. It has proven successful in screening for G protein-coupled receptor-binding compounds, protein interaction inhibitors, lead compounds for the development of treatments for various diseases, and more.
• What factors need to be considered when designing DEGLs?
  • The diversity and quality of DEGLs can affect hit rates. Considerations to be taken into account when designing include the diversity of compound library structures, types of biological targets, methods of library synthesis, screening strategies for binding compounds, etc.

CD BioGlyco has the greatest diversity of DEGL libraries and offers customized DEGL screening solutions for the discovery of protein-templated ligands. Please feel free to contact us to discuss detailed DEGL screening solutions. We will utilize our reliable and efficient screening process and state-of-the-art platforms to best support your research!

• Magnetic Bead-based DEGL Affinity Screening
• Resin Tip-based DEGL Affinity Screening
• Interaction-dependent PCR (IDPCR)-based DEGL Screening
• DNA Photoaffinity Labeling-based DEGL Screening
• Microfluidic Processor-based DEGL Screening
• Cell-based DEGL Screening
• DNA Programmed Affinity Labelling (DPAL)-based DEGL Screening
• DEGL Screening for Glycan-Protein Interaction Study
• DEGL Screening for Protein-Protein Interaction Inhibitor Discovery
• DEGL Screening for G Protein-coupled Receptor-Binding Compounds Discovery
• DEGL Screening for Protein Ubiquitination Study
• DEGL Screening for Bacterial Enzyme Study
• DEGL Screening for Antibody Target Identification