Overview

G protein-coupled receptors (GPCRs), the largest superfamily of human membrane target proteins, are important regulators of numerous physiological processes. They are associated with many diseases and are important drug targets. A variety of drugs have been developed using them as targets. It is found that sugar molecules can act as ligands for GPCRs and activate G protein-mediated signaling pathways by binding to specific receptors, thereby regulating cellular physiological functions. For example, glucose can regulate glucose metabolism and insulin secretion by interacting with certain GPCRs. At CD BioGlyco, we provide professional and customized DNA-encoded glycan library (DEGL) High-Throughput Screening (HTS) solutions to discover GPCR-binding compounds. Through the discovery of GPCR-binding compounds, we help advance the discovery of drug-lead compounds, the study of cellular processes, and the development of therapeutics.

Your Trusted Partner for DEGL Screening for GPCR-binding Compounds Discovery

We have conducted in-depth studies on DEGL screening for GPCR binding compounds and optimized multiple screening methods for GPCR ligand discovery. The main strategies include purified protein-based, membrane preparation-based, and cell-based DEGL screening.

• In purified protein-based DEGL screening, we use different methods to stabilize GPCRs, including nanodisc, detergent, etc.
• Membrane preparation-based DEGL screening is an alternative approach that maintains the conformation of GPCRs, provides higher target density, and omits the step of purifying proteins from membranes.
• Cell-based DEGL screening is used to target GPCRs and has been validated. The cell lines used therein all overexpress GPCR targets.

Our DEGL screening protocols for GPCR binding compound discovery are fully customized. After understanding the experimental needs of our clients, we combine a variety of advanced technologies to provide one-stop services such as target protein production, DEGL molecular library construction, affinity screening, custom synthesis of active compounds, and bioactivity validation. The specific experimental process is as follows:

Library Design and Construction

We design customized DEGLs, synthesize glycans of different structures, and combine them with unique DNA sequences to construct DEGLs. We synthesize libraries of compounds of various orders of magnitude to maximize hit rates.

Library Screening

Cells or GPCRs are incubated with DEGLs. Compounds that bind to the GPCR target are retained and non-binding compounds are washed out. The eluted samples are then subjected to polymerase chain reaction (PCR) amplification to add specific sample-identifying sequencing adapters to facilitate sequencing.

Next-generation Sequencing (NGS)

After screening, DNA barcodes of retained compounds are sequenced to identify glycan structures that interact with GPCR targets.

Data Analysis and Hit Validation

We have efficient bioinformatics tools to parse the data and identify hit compounds. Then we synthesize the off-DNA compounds and carry out subsequent analysis and validation of biological activity. The validation involves the hit compounds being characterized in more detail to understand their binding kinetics, selectivity, etc. In addition to this, we evaluate their biological activity.

Workflow

We offer a full range of solutions including the custom-synthesis of DEGLs and screening against GPCR targets to discover compounds that bind to them with high affinity.

Applications

• DEGL screening is useful to help discover new binding ligands for known GPCRs with high specificity and affinity and novel drugs with therapeutic potential.
• The ligand binding of some orphan GPCRs (oGPCRs) is currently undefined. DEGL screening helps to contribute to the discovery of ligands for these oGPCRs and advances the study of their signaling mechanisms.
• DEGL screening provides valuable information on the mechanism of GPCR-ligand interactions and helps to better understand the structural requirements for GPCR binding and activation.

Advantages

• We employ different DEGL screening strategies for the discovery of GPCR binding compounds, including membrane-based DEGL screening and DEGL screening of purified proteins.
• We have the ability to synthesize DEGLs of various orders of magnitude. Among them, the diversity of DEGL screening molecules helps to maximize the hit rate, especially for oGPCRs.
• Based on extensive practical experience, our DEGL screening and hit validation experiments for GPCR binding compound discovery run efficiently.

Publication Data

Frequently Asked Questions

• Why is it important to control the quality of GPCRs in DEGL screening?
  • DEGL screening requires fewer GPCRs than other screening methods and requires highly correctly folded proteins to be effective. Incorrectly folded proteins can produce misleading binders, thus reducing the quality of the screen. Therefore, strict quality control of GPCRs can help to greatly increase the success rate of DEGL screening.
• What is the cycle time for DEGL screening and hit validation?
  • The experimental cycle time for DEGL screening for GPCR binding compound discovery varies depending on the complexity of the project. Typically, the entire screening process and hit validation is completed in a few weeks to a few months. Specific project cycle timesheets will be provided at the time of experimental protocol communication.

GPCRs are a class of proteins that are important in drug discovery and development. CD BioGlyco offers customized DEGL screening solutions for the discovery of GPCR-binding compounds. We aim to support the discovery of GPCR-binding compounds and the development of novel drug candidates targeting GPCRs by exploring glycan structures in a high-throughput and efficient manner. Please feel free to contact us for the customized DEGLs and detailed screening and validation process.

• 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 Protein Ubiquitination Study
• DEGL Screening for Bacterial Enzyme Study
• DEGL Screening for Antibody Target Identification
• DEGL Screening for Protein-templated Ligand Discovery