DNA-encoded Single-Pharmacophore Glycan Library

DNA-encoded Single-Pharmacophore Glycan Library

Overview of DNA-encoded Single-Pharmacophore Glycan Library

DNA-encoded glycan library (DEGL) is an up-and-coming tool for compound discovery, featuring an incredibly convenient and rapid way to screen out target compounds efficiently and shorten the project cycle. CD BioGlyco gives you access to leading DEGL experts who work with you to understand your discovery objectives and guide you in DEGL Design, Construction, and High-throughput Screening. We provide professional DEGL encoding strategies such as single-pharmacophore, Dual-Pharmacophore, and Trio-Pharmacophore.

DNA-encoded Single-Pharmacophore Glycan Library Holds Exponential Possibilities

In single-pharmacophore libraries, no matter how complex the individual chemical parts are coupled to unique DNA segments (single-stranded or double-stranded forms).

DNA-recorded Synthesis

Relying on the use of split-and-pool procedures, CD BioGlyco uses DNA-recorded synthesis to construct a DNA-encoded single-pharmacophore glycan library. We build libraries through a series of chemical transformations and multiple steps.

  • Our professional researchers first bind a set of specific DNA sequences to small organic molecules by chemical ligation, and these compounds with deoxyribonucleic acid are first combined (Pool) and homogenized (Split) into a certain number of groups.
  • Under similar conditions, the building blocks of the second group are combined with the first group by enzymatically linking the oligonucleotide strands coding for the modifications corresponding to the compounds of the second group before mixing them.
  • The other group is for the oligonucleotide encoded by the second modification, which is enzymatically introduced before mixing. This cycle is repeated several times, and our researchers provide single-pharmacophore glycan library construction services for DNA-encoded compounds with specific sizes.

Schematic representation describing encoding procedures for DNA-recorded glycan libraries. (CD BioGlyco)

DNA-templated Synthesis

We design and construct new single-pharmacophore glycan libraries using a pool of pre-coded DNA templates. Based on the principle of base complementarity in DNA double-stranding, our researchers join a long single-stranded DNA sequence to a first set of small-molecule compounds. Several subsequent merging and homogenization processes rely on DNA-directed chemical reactions to facilitate the coupling of different building blocks to obtain macrocyclic coding compounds.

Schematic representation of the encoding strategies for DNA-templated synthesis of glycan libraries. (CD BioGlyco)

Workflow

Based on the mature DNA-encoded library (DEL) synthesis process and quality control system, we provide efficient and high-quality design and construction of DEGL. Our researchers follow the whole process. Our service process includes single pharmacophore design, synthetic method selection and optimization, glycan library synthesis, validation, affinity screening, and data analysis.

Flowchart of DEGL development. (CD BioGlyco)

Applications

  • DNA-encoded single-pharmacophore glycan library can be used for the discovery of small molecule ligands to protein targets of biological and pharmaceutical interest.
  • Single-pharmacophore libraries allow researchers to study the role of specific glycan structures in drug interactions.
  • The DNA-encoded single-pharmacophore glycan library allows for rapid and high-throughput screening of thousands of glycan variants and identifies the potential glycan leads.

Advantages of Us

  • CD BioGlyco offers custom glycan library development services. Hundreds of DEGL molecules are rapidly derivatized and synthesized based on specific compound structure types.
  • Relying on our strong synthetic capabilities, we offer DEGLs with novel chemical structures, broad spatial coverage, and drug-like molecular properties.
  • Based on a strict quality control and validation system, we ensure to provide the most perfect glycan library for our clients.

Publication Data

Technology: DNA encoded library (DEL) synthesis, Crimped Head-Piece, crosslinking, High-performance liquid chromatography (HPLC) purification, Liquid chromatography-mass spectrometry (LC-MS), Next generation sequencing

Journal: Bioorganic & Medicinal Chemistry

Published: 2024

IF: 3.3

Results: In this study, researchers designed a new Head-Piece structure to improve the efficiency and accuracy of existing DEL systems. The researchers synthesized Crimped Head-Pieces using a crosslinking approach, which increased the diversity of molecular identifiers and the flexibility of binding sites, thereby enhancing the screening of molecules in the library. This double-stranded functional Head-Piece can be used to generate single or dual pharmacophore libraries. Optimized synthetic routes and multiple validations indicate that the Crimped Head-Piece plays a key role in DEL construction.

Fig.1 Sequence and structure of the Crimped Head-Piece design.Fig.1 Schematic design of the Crimped Head-Piece. (Rama-Garda, et al., 2024)

Frequently Asked Questions

  • How to design a DEGL?
    • DEGL design is the combination of mono-, bi-, and tri-functional molecular blocks with DNA-compatible reactions. The diversity of library compounds is mainly derived from the diversity of molecular blocks and new DNA-compatible reactions.
  • What single-pharmacophore glycan library construct methods does CD BioGlyco offer?
    • DNA-recorded synthesis
    • DNA-templated synthesis
    • DNA-routing synthesis
    • Reactor method

CD BioGlyco delivers a full DEGL construct solution with the adaptability you need. We are committed to meeting our client's needs in all aspects of DEGL build quality indicators. To serve you better, our professional project management team will follow up on your DEGL construction service. Please feel free to contact us with any inquiries.

Reference

  1. Rama-Garda, R.; et al. Design, synthesis and validation of a new Crimped Head-Piece for DNA-encoded libraries generation. Bioorganic & Medicinal Chemistry. 2024, 99: 117596.
For research use only. Not intended for any clinical use.
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