Chemistry-driven DNA-encoded Glycan Library (DEGL) Design

Chemistry-driven DNA-encoded Glycan Library (DEGL) Design

Overview

DNA-encoded library (DEL) technology is an advanced technology that creates a tool for efficient screening and analysis by combining compounds with DNA encoding. Currently, DELs have made significant progress in drug discovery and biomarker research. Chemistry-driven DEGL design leverages the power of chemistry and DNA encoding to create a comprehensive library of glycans. This approach facilitates the systematic exploration of glycan structures and their biological interactions. By encoding glycans in DNA, researchers can efficiently synthesize and analyze vast libraries, ultimately delving into glycan function and discovery with unprecedented precision. This method stands as a cutting-edge tool in glycomics, offering a pathway to novel insights and applications.

Unlock the Ultimate Potential of Glycans with Chemistry-Driven DEGL Design

CD BioGlyco offers comprehensive DEGL Design, Construction, and Screening services, backed by advanced expertise and professional knowledge. Among them, we offer expert services in designing libraries driven by chemistry, utilizing our research on drug-like scaffolds and building blocks and novel DNA-compatible chemical reactions and synthesis schemes.

Start From Drug-Like Scaffolds and Building Blocks

During the design process, we fully consider the physicochemical properties (PCPs) and structural diversity of the compounds, as well as the actual preparation conditions. During the design process, we used different building block selection strategies and constraints to compare different compound library design schemes. Taking two kinds of two-cycle DEGL design schemes as an example, we design the building block of the two-cycle sugar libraries as amino acids + sugar molecules containing carboxyl groups and primary amines + sugar molecules containing carboxyl groups, respectively. By comparing the differences in PCPs and chemical space coverage between these two schemes, the effects of different building block selection strategies and constraints on chemical space sampling can be evaluated. By comparing the evaluation results, we help you to custom-design +the route of DEGL construction.

Start From Reported DNA-Compatible Chemical Reactions and Synthesis Schemes

DNA compatibility is also taken into account by our experts when performing library construction route design to ensure that the synthesized compounds are stable in connection with DNA barcodes and that the affinity of the compounds is not compromised. We combine the reported DNA-compatible chemistry and the construction schemes that have been used to build DEGLs and perform the structure and construction strategy design of DEGLs for you.

Workflow

Flowchart of chemistry-driven DEGL design. (CD BioGlyco)

Applications

  • DEGL design can help systematically explore the structure-function relationship of glycan molecules and help reveal the biological roles of glycans in cellular recognition, signaling, and disease genesis.
  • Researchers design construct and screen glycan libraries to gain insight into the effects of glycan modifications on biological functions and interactions.
  • The design of DEGLs is used to construct and screen libraries of compounds capable of binding specifically to glycan molecules for specific biological targets, leading to the discovery of potential drug candidate molecules.

Advantages

  • Our DEGL design service can accurately correlate the chemical structures of glycan molecules with their biological functions, helping to reveal the biological roles and mechanisms of glycan molecules.
  • Our chemistry-driven approach is designed to be able to generate libraries of glycan molecules with broad diversity, covering a wide range of glycan structures and modifications, thereby improving coverage and screening comprehensiveness of target molecules.
  • Our chemistry-driven design and construction of DEGLs containing millions of glycan molecules make it possible to perform large-scale screening in a short period.

Publication Data

Technologies: DEL technology, Uniform manifold approximation and projection (UMAP) technique

Journal: Journal of Chemical Information and Modeling

Published: 2024

IF: 5.6

Results: This article discusses a building block-based approach to DEL design. The researchers analyzed the constraints of combinatorial library design, including the number of chemical cycles, bonding construction strategy, and building block class selection, to seek the ideal library design. They compared library designs for two cycles and considered PCPs and chemical space coverage under different building block selection strategies and constraints. It was found that widely available amines and acids are essential to enable extensive exploration of the chemical space. By visualizing the commonly used building block set in reduced dimensions using the UMAP technique, it is possible to demonstrate the impact of different building block selection strategies on the properties of the final output library.

Fig.1 UMAP technologies are utilized for the analysis of Fmoc-protected amino acids, primary amines, and carboxylic acid derivatives. Fig.1 Analysis of Fmoc-protected amino acids, primary amines, and carboxylic acid derivatives by using UMAP technologies. (Fitzgerald, et al., 2024)

Frequently Asked Questions

  • How is DEGL different from traditional glycoconjugate libraries?
    • DEGL has some significant differences in design and technology from traditional glycoconjugate libraries. Each glycoconjugate in DEGL is associated with a unique DNA sequence, which allows for easier tracking and identification of specific compounds during the screening and identification process.DEGL can also be screened and analyzed by High-Throughput DNA Sequencing technology which accelerates and simplifies the process of compound identification. In addition, DEGLs are often designed with chemical reaction feasibility and efficiency in mind, increasing utility, while creating a more diverse structural space by introducing different sugar groups, linkages, and modifiers to increase compound diversity and biological activity. Conventional glycan libraries usually do not have these features.
  • How does DEL technology utilize DNA coding for glycoconjugate tracking and identification?
    • Each glycoconjugate in DEGL is associated with a unique DNA sequence, which allows for easier tracking and identification of specific compounds during screening and identification. Each glycoconjugate has its own unique DNA barcode, and by recognizing these DNA barcodes the location and presence of specific compounds in the mixture can be easily tracked. During the screening process, high-throughput DNA sequencing technology can be used to analyze the DNA barcodes in the DEGL to determine the identity and nature of individual compounds. This allows for rapid and accurate identification of compounds of interest.

CD BioGlyco offers advanced technology and a team of specialized personnel to provide comprehensive chemistry-driven DEGL design services. We hope that our expertise will contribute to your research in new drug development. If you are interested in our services, please feel free to contact us!

Reference

  1. Fitzgerald, P.R.; et al. Building block-centric approach to DNA-encoded library design. Journal of Chemical Information and Modeling. 2024.
For research use only. Not intended for any clinical use.
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