DNA-Compatible Reaction Development

DNA-Compatible Reaction Development

Overview of DNA-Compatible Reaction Development

The main goal of DNA-compatible reaction development is to design and optimize chemical reactions that are compatible with DNA molecules used in the construction of DNA encoded library, allowing for efficient and safe chemical transformations during DNA manipulation and handling. Current research focuses on developing chemical reactions that have high selectivity and low toxicity to DNA molecules, which require effective chemical transformations while maintaining the integrity of the DNA structure. Additionally, the use of novel catalysts is an important advancement in this field, significantly improving the control of the reaction and the purity of the product.

Unlock Precision with Our DNA-Compatible Reaction Development

CD BioGlyco provides professional DNA-encoded library (DEL) technology to build DNA-encoded glycan libraries (DEGL) for our clients, and we also offer DNA-compatible reaction development services used in DEGL Construction. The DNA-compatible reaction development services are divided into two parts: DNA-compatible functional group transformation development and DNA-compatible bond formation development.

Our DNA-compatible reaction development service. (CD BioGlyco)

Workflow

Scheme Design

First, our experts communicate with our clients to clearly define the specific goals of the DNA-compatible reactions they need to develop, such as glycan compound modification and cross-linking. We then discuss the requirements of the target reactions, including the type of glycan compounds, the selectivity and specificity requirements of the reactions, and the DNA compatibility standards.

Reaction Development

After that, we select and design the reaction type for bond formation, including but not limited to the formation of C-C bonds such as C(2)-sp, C(sp2)-sp2, C(sp2)-sp3, and C(sp3)-sp3. This also includes the formation of C-X bonds, such as C-N, C-O, C-S, C-P, and C-Se, to ensure that the reaction is DNA-compatible. Meanwhile, we also develop DNA-compatible functional group transformations, designing reaction conditions that are compatible with DNA. Then, we select mild catalysts and substrates and choose non-transition metal catalysts or other catalysts that are friendly to DNA, such as copper, nickel, or other green chemical catalysts. Subsequently, we establish mild reaction conditions, such as low temperature, moderate pH value, and appropriate solvents, to ensure the stability of DNA.

Reaction Condition Optimization

Finally, We verify whether the reactions are stable for DNA, ensuring that the reaction process does not degrade or have adverse effects on DNA. At the same time, we use appropriate analytical techniques to test the conversion effects of sugar compounds in the reaction, detect the purity of the reaction products, and ensure the quality and correctness of the product.

Applications

  • The development of more applicable DNA-compatible reactions for the synthesis of DELs will allow for the introduction of thousands more compounds into compound libraries and simultaneous screening, thus speeding up the drug discovery process.
  • Specific chemical probes are synthesized using DNA-compatible reactions for the identification and quantification of specific DNA sequences. These probes can be used for gene expression studies and molecular detection.
  • Reverse screening of optimized compounds can help researchers identify more promising compounds and advance the drug development process.

Advantages

  • DNA-compatible reactions allow a large number of compounds to be processed simultaneously in a single reaction system, enabling high-throughput screening through binding to DNA code, which can greatly increase research efficiency.
  • DNA-compatible reactions are designed with DNA protection in mind to minimize damage to the structure and function of the DNA molecule by chemical reactions.
  • DNA-compatible reactions allow the construction of libraries containing a large number of compounds with different chemical structures and functional groups, thus providing a wide chemical space for screening and optimization.

Publication Data

Journal: Frontiers in Chemistry

Published: 2022

IF: 3.693

Results: This article describes a DNA-compatible Suzuki-Miyaura cross-coupling reaction for the synthesis of DEL. The researchers used aryl iodides and (hetero) aryl boronic acids for the reaction and successfully achieved the synthesis of DNA-encoded compounds. The main finding is that this reaction condition allows aryl iodides and (hetero) aryl boronic acids to react efficiently in a coupling reaction to produce the target compounds. This approach provides an efficient strategy for the synthesis of DNA-encoded compounds.

Fig.1 Suzuki-Miyaura cross-coupling reaction occurs between on-DNA compounds 1a and heteroaryl boronic acids. Fig.1 Heteroaryl boronic acids react with on-DNA compounds1a. (Siripuram, et al., 2022)

Frequently Asked Questions

  • What are the challenges of DNA-Compatible Reactions?
    • Selectivity and specificity: Ensuring that the reaction conditions are selective and specific for DNA and avoiding unwanted side reactions.
    • Stability: Maintaining the stability of the DNA compound complex during reaction and storage.
  • How do you ensure that DNA-Compatible Reactions do not disrupt the structure and function of DNA?
    • Mild reaction conditions (e.g., low temperatures, moderate pH) are chosen to avoid DNA damage from high temperatures or extreme pH. DNA is usually stable in neutral or near-neutral environments, so strong acid and base conditions should be avoided.
    • Reaction time should be shortened to reduce the amount of time the DNA is exposed to the reaction conditions, thus reducing potential damage to the DNA.
    • DNA-friendly cross-linking agents, such as low-reactive chemical cross-linkers, are used to avoid irreversible damage to the DNA structure.

At CD BioGlyco, we provide cutting-edge DNA-compatible reactions tailored to enhance your research and development processes. Our expertise ensures that chemical reactions are optimized to maintain DNA integrity, utilizing mild conditions to prevent potential damage from extreme environments. If you are interested in our service, please feel free to contact us!

Reference

  1. Siripuram, V.K.; et al. DNA-Compatible Suzuki-Miyaura cross-coupling reaction of aryl iodides with (hetero) aryl boronic acids for DNA-encoded libraries. Frontiers in Chemistry. 2022, 10: 894603.
For research use only. Not intended for any clinical use.
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