DEGL Screening for Protein Ubiquitination Study

DEGL Screening for Protein Ubiquitination Study

Overview of DNA-encoded Glycan Library (DEGL) Screening for Protein Ubiquitination Study

Protein ubiquitination and subsequent degradation are involved in various aspects of the regulation of eukaryotic cell function. Excessive degradation or inability to clear proteins may lead to many human diseases such as cancer, brain disorders, etc. Therefore, the development of therapeutic approaches targeting the ubiquitin-proteasome system has attracted much attention. DEGL screening, as an effective and widely used method for identifying ligands that regulate protein ubiquitination, plays an important role in studying the mechanism of protein ubiquitination and potential therapeutic targets for related diseases. CD BioGlyco offers customized and flexible DEGL screening solutions to find small molecule inhibitors or activators of protein ubiquitination, providing reliable support for protein ubiquitination studies.

In-depth Exploration of Protein Ubiquitination Through Our Customised Strategy

We offer customized screening strategies to ensure the successful screening of compounds that induce or inhibit protein ubiquitination. The diversity and high quality of DEGLs used for screening maximize the hit rate. With our extensive experience in protein ubiquitination machinations and High Throughput Screening of DEGLs, the entire screening process is simpler to design and conduct. The specific experimental flow is as follows:

DEGL Design and Construction

We are at the forefront of science and have a dedicated DEGL synthesis team responsible for various DNA-compatible compounds. After understanding the experimental needs of our customers, we provide customized DEGL solutions, deriving and synthesizing various orders of magnitude of DEGs according to specific compound structure types.

DEGL Screening

DEGL screening enables the screening of hundreds of millions of compounds in a single run, with a small amount of target proteins and a much shorter screening cycle. We incubate DEGL with the target and elute it in different ways based on the affinity binding of small molecules to proteins. Non-binding small molecules are removed and a high enrichment of small molecule ligands with high affinity is achieved.

  • The target proteins to be screened are pre-fixed and the fixed proteins are subsequently incubated with DEGL.
  • Molecules that bind weakly to the protein target or do not bind to the protein are washed away.
  • Enrichment of high-affinity small molecules is achieved by eluting the protein-bound molecules.
  • We amplify the DNA tags of the protein-bound molecules by PCR.

Next-generation Sequencing (NGS) and Data Analysis

The DEGL screening data contains information to explore protein ubiquitination and optimize the direction of compounds that induce or inhibit protein ubiquitination. We sequence the amplified DNA tags and decode the compound information based on the DEGL DNA tags.

Hit Validation and Evaluation

We select representative theoretical end-product molecules for validation and evaluation. Combining various analytical techniques such as X-ray crystallography and surface plasmon resonance, we perform relevant physical and biochemical analyses, functionality, and lead compound optimization.

Workflow

Our experienced team communicates in detail with clients to customize the appropriate DEGL screening strategy for protein ubiquitination studies. Multiple selection and in-depth data analysis ensure that the identified compounds are selective for the target protein.

Flowchart of DEGL screening for protein ubiquitination. (CD BioGlyco)

Applications

  • DEGL screens are used to identify inhibitors and activators that regulate protein ubiquitination, providing valuable structural information for the development of protein degradation agents.
  • DEGL screens provide insight into the mechanisms that regulate protein ubiquitination.
  • DEGL screens are used to identify compounds that regulate the process of protein ubiquitination, thus providing valuable information for the development of new chemical probes or potential drug candidates targeting the ubiquitination pathway.

Advantages

  • Total solution: We provide a total DEGL screening solution, including protein expression and purification, DEGL screening, hit compound validation, and evaluation.
  • High-quality and differentiated DEGL: We utilize novel DNA-compatible chemistries and innovative library-building strategies, employing a large number of novel and specific synthetic building blocks accumulated over the years on our chemistry platform.
  • Rapid experimental cycle: We have extensive research experience in DEGL screening and protein ubiquitination, which greatly shortens the DEGL custom synthesis and screening cycle.

Publication Data

Technology: DNA encoding library (DEL) screening

Journal: ChemMedChem

IF:3.54

Published: 2021

Results: In this paper it is indicated that several compounds targeting an E3 ubiquitin ligase were obtained by DEL screening. These compounds can be used as tools to probe the interaction between ubiquitin ligases and the transcription factors responsible for degradation.

Frequently Asked Questions

  • What is the relevance between protein ubiquitination and disease?
    • Protein ubiquitination plays a vital role in regulating various cellular processes such as signal transduction and protein degradation. Dysregulation of protein ubiquitination has been implicated in the pathogenesis of a variety of diseases, such as cancer and neurodegenerative diseases. For example, in cancer dysregulation of the degradation of cell cycle regulatory proteins leads to uncontrolled cell growth and cancer development.
  • How does DEGL screening differ from other methods for studying protein ubiquitination?
    • DEGL screening offers significant advantages in the study of protein ubiquitination. The technique serves as a high-throughput and efficient screening method allowing the screening of a large number of glycan ligands in a single experiment, thus accelerating the identification of compounds that regulate protein ubiquitination.

CD BioGlyco provides strong support for exploring mechanisms of protein ubiquitination regulation and drug development for diseases associated with protein ubiquitination dysregulation through high-throughput DEGL screening. Our DEGL screening experts will assess your research needs and develop appropriate and optimized solutions. Welcome to contact us to discuss DEGL screening to accelerate protein ubiquitination research.

Reference

  1. Kunig, V.B.K.; 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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