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

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

Overview

Glycans, as important biomolecules in living organisms, are involved in intercellular recognition, immune responses, pathogen infections, and many other biological processes. However, the complex and highly diverse structures of glycans make their study challenging. DNA coding technology allows each glycocompound to be labeled with a specific DNA sequence, and this labeling not only provides an efficient method for compound identification and tracking but also makes it possible to perform large-scale screening in a single experiment. Our combination of biologically-driven design concepts allows us to customize compound libraries according to specific biological targets, thereby increasing the relevance and efficiency of screening.

Precision DEGL Design for Cutting-Edge Research

CD BioGlyco has a wealth of experience in delivering expert DEGL Design Services to our clients. We provide thorough DEGL design services from various angles tailored to your specific requirements, encompassing a range of options such as Chemistry-driven DEGL Design, biology-driven DEGL design, and Artificial Intelligence (AI)-based DEGL Design. The details of the biology-driven DEGL designs service at CD BioGlyco are as follows.

Target Structure Analysis

To begin with, our experts engage in thorough communication with you to determine the specific biological target for study and analyze its structure according to your requirements.

  • If the target of interest has been well documented in the literature, we analyze the three-dimensional (3D) structural information and potential binding sites. Then, we select the optimal building block in conjunction with compounds known to readily bind to the target's reported pocket.
  • If the target under study is inadequately documented in the literature, we employ advanced techniques such as protein X-ray crystallography data to obtain and analyze the 3D structural information of the target. This enables us to accurately identify potential binding sites and key interaction regions, providing crucial references for subsequent drug design and development. Additionally, a comprehensive functional analysis of the target is conducted to gain a better understanding of its biological properties and potential mechanism of action.

DEGL Design

We design DEGL based on detailed structural information of the biology target, utilizing 3D structural data to identify and localize potential binding sites. Building blocks containing specific functional groups or chemical moieties that bind well to the target are screened based on these sites. Advanced drug design software is used for validation to ensure that the building blocks screened for library construction have desirable binding properties and biological activities. The software can simulate compound interactions with the target and computationally predict their binding affinity and stability.

Workflow

Workflow of biology-driven DEGL. (CD BioGlyco)

Applications

  • Glycan modifications on the surface of cancer cells are often associated with cancer. DEGL can help identify these characteristic glycan molecules for early cancer surveillance.
  • DEGL can be used to study the interaction of glycans with immune cells or immune molecules, thereby facilitating the development of vaccines and immunotherapies.
  • DEGL can be used to screen glycan molecules and for the development of glycan biomaterials with specific functions, such as drug delivery systems, tissue engineering scaffolds, etc.

Advantages

  • DEGL is widely used in drug discovery, immunology, cancer research, infection research, and other fields, promoting cross-fertilization and technological innovation in various disciplines.
  • DNA is highly stable and durable as a coding carrier, making constructed DEGLs suitable for long-term storage and use.
  • We adapt the size and composition of the libraries to the research needs and flexibly design glycan libraries with specific objectives, thus adapting to different research and application scenarios.

Publication Data

Technologies: DNA-encoded libraries (DELs)

Journal: Journal of Chemical Information and Modeling

Published: 2023

IF: 4.956

Results: This article focuses on how selection data from DELs can be analyzed to predict the ability of untested building blocks to bind to target substances. The article describes a method of analysis based on the construct level to determine whether compounds bind to the target substance through interpretive analysis of individual constructs and quantification of interactions between constructs. Also, the article utilizes similarity scoring methods to predict the productivity of new building blocks and compares the capabilities of different similarity metrics. Finally, the article develops a model that combines the behavior of the building blocks at each position to statistically predict the probability of an untested molecule binding to the target substance. The article also mentions that while the results of the study are based on specific DELs and target substances, this informatics workflow can be extended to analyze the results of other DEL studies.

Fig.1 The number of potential compatible partners varies depending on the binding probability of each building block. Fig.1 The number of compatible potential partners varies based on the binding probability for each building block. (Zhang, et al., 2023)

Frequently Asked Questions

  • What are the advantages and limitations of DEL technology over traditional methods?
    • DEL technology is a DNA-encoded method that allows the preparation and screening of millions of diverse compounds in a single experiment. Relative to traditional methods, DELs offer lower costs and faster screening speeds, allowing for extensive exploration in chemical space. However, due to the large combinatorial scale of DELs, selection data are often noisy, including variations in reaction yields, formation of truncations, errors in the experimental process, and noise in DNA sequencing. Therefore, to improve the signal-to-noise ratio, selection data need to be analyzed using computational models.
  • Is DEGL design suitable for all types of glycan studies?
    • The DEGL design is well suited for studies that require screening of a large number of different glycan molecules, especially in drug development, target identification, and biomarker discovery. For studies that require the exploration of complex glycan structures and glycosylation patterns, DEGLs can provide structural diversity and high-precision screening capabilities. However, its effectiveness may be limited by the structural complexity of glycans, so in some cases, we also combine it with other methods for joint analysis and design.

CD BioGlyco's biology-driven DEGL design services offer specialized guidance from a comprehensive perspective and are utilized by clients globally. We have full confidence that our experts will significantly contribute to the advancement of your research. Please feel free to contact us if you are interested in our service!

References

  1. Zhang, C.; et al. Building block-based binding predictions for DNA-encoded libraries. Journal of Chemical Information and Modeling. 2023, 63(16): 5120-5132.
  2. 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.
Related Solutions
Inquiry

Our mission is to provide comprehensive solutions for glycan research, from library design and high-throughput screening to detailed data analysis and validation.

Get In Touch
  • twitter
Copyright © CD BioGlyco. All Rights Reserved.
Top