High-throughput Screening (HTS) of DNA-encoded Glycan Library (DEGL)
Overview of High-throughput Screening (HTS) with DNA-encoded Glycan Library (DEGL)
In the field of chemical biology and drug discovery, the pursuit of small organic ligands with selective binding to targets remains a towering challenge. Conventional HTS of chemical libraries, despite its groundbreaking nature, is hampered by logistical constraints and prohibitive costs, restricting its scope and efficacy. The emergence of HTS with DEGL marks a transformative shift in this landscape. Inspired by the success of encoded biomacromolecule libraries, DEGLs leverage DNA barcodes to explore the expansive realm of glycan-protein interactions. With libraries potentially encompassing billions of compounds, DEGLs overcome traditional HTS limitations, presenting a scalable solution for identifying high-affinity, specific ligands.
Unlocking Glycan Secrets: Revolutionize Drug Discovery with DEGL
At CD BioGlyco, we're excited to offer HTS using DEGL which represents the latest in integrating chemistry, biology, and pharmaceuticals for discovering and researching new therapeutics. This innovative approach harnesses the power of DNA barcoding to facilitate the efficient discovery and optimization of glycan molecules that interact with specific biological targets. By combining the advantages of DNA encoding with HTS techniques, our service enables rapid and comprehensive identification of promising glycan candidates from an extensive glycan library, thereby propelling forward drug discovery and fundamental biological research.
Workflow
Our workflow for HTS utilizing DEGL typically encompasses the following sequential steps:
Library Construction
To begin with, we employ diverse synthesis techniques to covalently link diverse glycan structures with unique DNA sequences, thus constructing an extensive DEGL. Each DNA sequence serves as a distinctive "identifier" for its corresponding glycan, facilitating subsequent recognition and tracking. We utilize both Solid Phase and Liquid Phase methods to customize libraries of varying sizes and types, tailored precisely to client specifications. This customization includes various quantities and types of libraries, aligning with specific research needs and applications, including:
Library Screening
A target protein of interest is selected and is usually tagged with a suitable label. This tagged protein is then immobilized onto solid supports, such as streptavidin beads. The DEGL is introduced to the immobilized target protein. The glycan molecules interact with the target protein, and each glycan is traceable via its associated DNA sequence. We remove these unbound glycan molecules through a series of washing steps, isolating only those glycans that tightly bind to the target protein. These bound glycans, along with their associated DNA, are then eluted using methods such as altering pH or temperature. Our screening methods are divided into two parts.
By screening strategies:
By applications:
Subsequent Decoding and Data Analysis
We amplify the recovered DNA sequences using PCR and then subject them to high-throughput DNA sequencing. The decoding of these sequences enables the identification of glycans with high binding affinity. Sequencing data is analyzed to pinpoint and select glycans that exhibit strong affinity for the target protein. The selected glycans are then employed in subsequent research and applications.
Publication Data
Technology: HTS, High-performance screening (HPS), DEL
DOI: org/10.1016/j.tips.2021.10.008
Journal: Trends in Pharmacological Sciences
Published: 2022
IF: 13.9
Result: In this study, the authors discussed the evolution and background of HTS and HPS technologies, emphasizing the limitations of traditional HTS methods, such as high costs, limited molecular testing, and high false-positive rates. They highlighted how HPS, particularly through DEL technology, offered significant advantages over HTS by enabling extremely large library sizes, efficient screening methods, and improved structure-activity relationship studies. The authors also explored the complexity of DEL technology, its diverse applications in drug discovery, and its potential future impact, including integration with HTS and computational simulations, as well as its role in drug repurposing, addressing emerging biological threats, and personalized medicine. This paper highlights the considerable potential and advantages of leveraging DEL technology within drug discovery. By presenting a more efficient and novel screening paradigm, it anticipates that ongoing advancements in HPS will increasingly influence future drug development, paving the way for the advent of groundbreaking pharmaceutical innovations.
Applications
- HTS of DEGL can be used for uncovering potential glycan-based drug candidates, especially within fields such as antiviral, anticancer, and immunomodulatory research.
- HTS of DEGL is useful for investigating glycan interactions with biological targets and provides a deeper understanding of glycoscience mechanisms.
- HTS of DEGL is applied for identifying specific glycan molecules that bind to pathogen surface glycans and supports the design and development of vaccines.
Advantages
- By merging DNA barcode technology with HTS, we offer a cutting-edge solution that enhances the efficiency of discovering and optimizing glycan interactions with biological targets.
- We possess the ability to construct compound libraries encompassing millions of entities, providing scalable solutions for identifying high-affinity specific ligands.
- We offer various types of DEL, such as natural sugar libraries, modified sugar libraries, glycan antigen libraries, and glycopeptide libraries, which can be customized according to specific client needs, supporting a wide range of research applications.
Frequently Asked Questions
- What are the advantages of HTS of DEGL?
- Extensive screening capabilities: The DEGL technology enables the concurrent evaluation of thousands of glycan molecules within a single experimental setup. Each glycan molecule is tagged with a distinct DNA barcode, which significantly enhances screening efficiency.
- Enhanced precision and efficiency: DEGL offers superior speed and accuracy in screening compared to traditional glycan library methods. This results in a more rapid identification and validation of glycan-target interactions.
- What methods can we use for data analysis?
- Negative binomial distribution-assisted data analysis
- Data aggregation method-assisted data analysis
- Z-score enrichment metrics-assisted data analysis
CD BioGlyco is devoted to delivering state-of-the-art glycan library screening services. Through our expertise and cutting-edge technology, we provide a basis for further investigation into the biological functions of these glycans and their potential therapeutic applications. Should you have any inquiries or require further details, do not hesitate to contact us. We eagerly anticipate collaborating with you to advance your research and drug development objectives.
Reference
- Sunkari, Y.K.; et al. High-power screening (HPS) empowered by DNA-encoded libraries. Trends in Pharmacological Sciences. 2022, 43(1): 4-15.
For research use only. Not intended for any clinical use.
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