DNA-encoded Glycan Macrocycle Library

DNA-encoded Glycan Macrocycle Library

Overview of DNA-encoded Glycan Macrocycle Library

The DNA-encoded glycan macrocycle library is an advanced molecular screening tool that combines DNA-encoding and glycochemical technologies to efficiently and sensitively identify and research interactions between glycan chains and biomolecules. The library can be used to screen diverse compound molecules by linking diverse glycan structures in the form of macrocycles to specific DNA sequences. In addition, the DNA-encoded glycan macrocycle library not only mimics the complexity of natural glycan chains but also enables High-throughput Screening and precise identification of target molecules by DNA sequences.

At CD BioGlyco, we have a dedicated DNA-encoded Glycan Library (DEGL) research team that provides custom DNA-encoded glycan macrocycle library construction services, covering the entire process from synthesis of the macrocycle, DNA tag ligation to final library screening.

Decoding Diversity: Unleash the Power of DNA-Encoded Glycan Macrocycles

Cyclization Strategies of Sugar Chains

The cyclization pathway of glycan chains usually involves N- to C-terminal linkages, end or side chain linkages, disulfide bonds, and all their possible combinations. During the construction of DNA-encoded glycan macrocycle libraries, the cyclization reaction of glycan chains must be compatible with DNA. Here, we develop diverse DNA-compatible chemical reactions to generate glycan macrocycle structures.

Several methods of sugar chain cyclization. (CD BioGlyco)

  • Copper-catalyzed azide/alkyne cycloaddition (CuAAC). CuAAC is a DNA-compatible chemical that can be used in the setup of various libraries of DNA-encoded compounds. To improve the efficiency of the CuAAC cycloaddition reaction for the synthesis of sugar chain macrocycles, we convert amines to azides and apply them in the macrocyclization of specific sugar chains.
  • Amide bond formation. Amide bond formation is by far the most used reaction in the DEGL field with a high degree of stability. The formation of amide bonds in DNA surface glycans limits the rotational freedom of their structure, resulting in a more efficient cyclization efficiency.
  • Thioether bond formation. By doping molecules with thio groups into the peptide structure, the addition of an electrophilic reagent in a specific solution containing the glycan causes them to undergo an affinity substitution reaction to form a thioether bond, thus fulfilling the goal of constructing a glycan macrocyclic structure on DNA.

Construction of DNA-encoded Glycan Macrocycle Library

In the construction of the DNA-encoded glycan macrocycle library, we use the synthesized glycan macrocycle structure as the backbone of the DNA-encoded molecular library. The cyclized glycan is anchored to the DNA strand and the constant macrocycle structure is diversely derivatized using a variety of amines with different structures as monomer building blocks, while each amine is encoded by a corresponding base pair DNA sequence. Subsequently, a library of DNA-encoded compounds containing members of larger orders of magnitude can be obtained by protection of functional groups, deprotection, and reactions with carboxylic acids and alkynes. The DNA-encoded glycan macrocycle library we have obtained is presented as a mixture of glycans and glycan affixes, and they are each encoded with a unique oligonucleotide sequence.

The construction scheme also includes using the molecular that are not glycan macrocle as the backbone and set glycopeptide as the building blocks of every cycle. After deprotection, cyclization, and other reactions form a glycopeptide macrocycle library. We provide custom DNA-encoded glycan macrocycle libraries by adapting the construction scheme of DNA-encoded glycan macrocycle libraries to your specific demand. At the same time, we also provide a DNA-encoded glycan macrocycle library with high-throughput screening for different compound molecules.

Workflow

The construction and screening of a DNA-encoded glycan macrocycle library combines modern molecular biology and chemistry synthesis methods. This makes screening more efficient and precise by linking glycan macrocycle molecules with unique DNA barcodes to form a large molecular library. Below is a workflow diagram of the DNA-encoded glycan macrocycle library construction and screening molecules we have produced for our clients, which shows a comprehensive overview of the key steps from library design to screening.

Flow of construction and application of the DNA-encoded glycan macrocycle library. (CD BioGlyco)

Applications

  • Targeted screening of drugs. DNA-encoded glycan macrocycle library can be used for high-throughput screening and rapid identification of high-affinity ligands for specific targets (e.g. proteins, enzymes, receptors), which can be applied to the development of novel drug molecules.
  • Biomarker identification. DNA-encoded glycan macrocycle libraries can be used to identify biomarkers associated with a particular disease.
  • Biological research. DNA-encoded glycan macrocycle library can be used to research the interactions between glycan chains and proteins, which can help to understand biological processes such as cell signaling and pathogen invasion.

Advantages

  • Our high-throughput DNA coding and molecular screening technologies enable the rapid construction of high-level DNA-encoded glycan macrocycle libraries for efficient and highly accurate molecular screening processes.
  • Our experts in synthetic chemistry, biochemistry, and molecular biology ensure highly professional support from the design of DNA-encoded glycan macrocycle libraries to their application.
  • We provide custom DNA-encoded glycan macrocycle library construction and screening services, as well as target-specific optimization to ensure that our client's research needs are met to the fullest extent.

Publication Data

Technology: UPLC-MS, diazonium transfer reaction

Journal: Molecules

IF: 4.2

Published: 2021

Results: In this research, the authors developed a method allowing the conversion of primary amines and anilines attached to DNA to their corresponding azides and found its potential application in DNA coding chemistry and macrocyclic DEL. The authors carried out research using DNA-labelled 6-aminohexanoic acid and DNA-labelled 4-aminobenzoic acid as model substrates for aliphatic amines and aromatic amines, respectively, and succeeded in constructing diazotransfer reactions attached to DNA. Meanwhile, the conversion rate and integrity of the DNA-bound products were employed to be analyzed by UPLC-MS. Immediately thereafter, the authors completed the synthesis of a macrocyclic DNA-encoded library by optimizing the reaction conditions of this reaction for [3+2]-cycloaddition. Through further analyses, the authors found that the diazotransfer reaction had a high conversion rate and was effective for most compounds.

Fig.1 Reactions for the synthesis of macrocyclic DNA-encoded libraries.Fig.1 Synthesis reactions for macrocyclic DNA-encoded libraries. (Ede, et al., 2021)

Frequently Asked Questions

  • What is a DNA-encoded glycan macrocycle library?
    • DNA-encoded glycan macrocycle library is a library of macrocyclic compounds generated using DNA-encoding technology combined with glycan biochemistry. It is a library in which each compound is linked to a unique DNA sequence, and each compound can be recognized and traced by the DNA sequence, thus achieving the goal of high-throughput screening.
  • What are the advantages of a DNA-encoded glycan macrocycle library?
    • The DNA-encoded glycan macrocycle library offers several advantages, such as:
    • High-throughput screening. Using DNA-encoded library technology, researchers can analyze millions to billions of different compounds in a single screening process, accelerating the drug discovery and biomarker identification process through high-throughput means.
    • Simplify subsequent analyses. Each compound is associated with a unique DNA sequence, making subsequent identification and analysis of active compounds by sequencing easier and more efficient.
    • Automation and standardization. Due to the standardization of DNA coding technology and automated processes, human error can be reduced and repeatability and reliability can be improved.

With an advanced technology platform and an exceptional team, CD BioGlyco provides custom DNA-encoded glycan macrocycle library construction services. With our innovative DNA-encoding technology and complex glycan macrocycle strategies, we provide the most reliable and efficient solutions to our clients. Please feel free to contact us if you are interested in DNA-encoded glycan macrocycle library.

Reference

  1. Ede, S.; et al. Improved diazo-transfer reaction for DNA-encoded chemistry and its potential application for macrocyclic DEL-libraries. Molecules. 2021, 26(6): 1790.
For research use only. Not intended for any clinical use.
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