DNA-compatible Bond Formation Development

Overview of DNA-compatible Reaction

DNA-compatible chemistry development aims to ensure compatibility with the DNA coding system by optimizing chemical reaction conditions. These technologies focus on the design and implementation of chemical reactions that are compatible with the DNA system for efficient labeling, recognition, and screening of compounds. These reactions ensure efficient binding and stability between the compound and the DNA tag during synthesis and processing. This approach allows the introduction of a wide range of chemically functional groups and structural units into DNA-encoded libraries (DELs), dramatically expanding the chemical space and range of applications. DNA-compatible bond formation development focuses on chemical bond formation in the DNA-encoded system, enabling the synthesis and optimization of complex molecules. This DNA-compatible reaction provides a wide range of chemical diversity under mild temperature and pH conditions while avoiding damage to fragile functional groups.

Seamlessly Connect with Our DNA-Compatible Bond Formation Development

CD BioGlyco provides professional hit-to-lead services for your drug development research, including not only the Design, Construction, Screening, and Hit Validation and Assessment of our DNA-encoded glycan library (DEGL) but also the development of DNA-Compatible Chemistries required in the DEGL library construction. The details of our DNA-compatible bond formation development are as follows.

C-C Bond Formation Development

C–C sp²-sp coupling development
C–C sp²-sp² coupling development
C–C sp²-sp³ coupling development
C–C sp²-sp³ coupling development

C(sp²)–X Bond Formation Development

C-N Bond Formation Development: We perform C-N coupling reaction development of on-DNA by different catalysts and substrates such as Buchwald t-butyl-XPhos precatalysts, aromatic amines, and aromatic bromides. This includes the development of C-N coupling reactions between different aromatic halide molecules of on-DNA with small molecules of aromatic amines, as well as reaction development of C-N coupling reactions between aromatic bromides on DNA and small molecules of aromatic amines.
C-O / C-S bond formation development: Our experts perform the development of C(sp²)-O and C(sp²)-S bond formation by proceeding through non-transition metal catalysts such as copper and nickel, as well as DNA-conjugated heterocyclic quaternary ammonium salts and thiols.
C-P bond formation development: We carry out the development of on-DNA C(sp²)-P bond formation through the reaction of DNA-conjugated aryl iodide with phosphonium chloride using a nickel catalyst in conjunction with the reference of reported literature.
C-Se bond formation development
C-S bond formation development

We perform the development of C-S bond formation by using metal-catalyzed reactions, reduction reactions nucleophilic substitution reactions, etc., and thiol substrates.

Workflow

Workflow of DNA-compatible Bond Formation Development. (CD BioGlyco)

Applications

In the development of glycan-based drugs, the development of DNA-compatible chemical reactions to build DEGLs can improve the chances of screening for biologically active glycan molecules.
To explore the interactions between glycan molecules and biological targets through high-throughput screening of glycoconjugate libraries, providing new directions and strategies for targeted drug development.
Sugar molecule design and development of glycan antigens from glycoconjugate libraries using DNA-compatible chemistry, which can be used for vaccine development and immunotherapy.

Advantages

DNA-compatible bond formation performs bonding reactions under conditions compatible with DNA systems, reducing instability and degradation during chemical reactions.
DNA-compatible bond formation supports the synthesis of diverse chemical structures that can handle different types of bonds and functional groups and also supports a wider range of chemical reaction types.
The development of DNA-compatible bond formation expands the variety of compounds that can be synthesized, providing a broad chemical space to explore new biological and chemical functions.

Publication Data

Journal: Bioorganic & Medicinal Chemistry

Published: 2021

IF: 3.3

Results: This article focuses on a large-scale screening of DNA-compatible reaction conditions, including Suzuki and Sonogashira cross-coupling reactions and reverse amide bond formation reactions. The study aims to optimize these reaction conditions and compare them with previously published methods. The authors tested the performance of 606 building units (including boronic acids, pinacol-boranes, and terminal alkynes), with 84% of the molecules having conversions above 70%. In addition, the authors describe effective experimental conditions for the formation of reverse amide bonding reactions starting from DNA derivatives carrying carboxylic acid groups and 300 primary, secondary, and aromatic amines. Reverse amide bonds are very common in DNA-encoded chemical libraries because of their excellent compatibility with DNA.

Fig.1 Diagram demonstrating the on-DNA Suzuki and Sonogashira cross-coupling reactions, along with the on-DNA reverse creation of amide bonds. Fig.1 Diagram illustrating on-DNA Suzuki and Sonogashira cross-coupling reactions, as well as on-DNA reverse formation of amide bonds. (Nicholas, et al., 2021)

Frequently Asked Questions

How does DEL technology work?
- DELs work by first synthesizing compounds or selecting the commercially available compounds, then binding each compound to a unique DNA tag. Subsequently, the compound library is constructed and detects compound-target interactions through high-throughput screening. Finally, detailed information about the compounds is obtained through decoding and analysis. This technique allows for simultaneous screening of a large number of compounds in a single experiment, improving screening efficiency and ensuring accurate labeling and tracking of compounds.
Are there new trends in the DEL technology?
- DEL technology continues to evolve, and the following are some of the major trends:
- Integration with other analytical techniques: DNA coding technologies are being integrated with other analytical techniques (e.g. mass spectrometry, single-cell analysis, etc.) to expand their applications and improve data resolution. These combinations enable efficient screening and analysis in more complex biological systems, providing more detailed and comprehensive data.
- Optimization of automation and high-throughput platforms: Advances in automation technology and high-throughput platforms have made the process of constructing and screening DELs more efficient. For example, the introduction of automated liquid handling systems and robotic screening systems has improved the efficiency and reproducibility of experiments, reduced manual operations, and increased the speed and accuracy of data processing.

CD BioGlyco is committed to providing you with top-notch DNA-compatible bond formation development services. With advanced technology and extensive experience, our team focuses on developing DNA-compatible chemical reactions to ensure efficient and stable synthesis for your biomolecular research and applications. Please feel free to contact us for more details!

References

Nicholas, F.; et al. Large screening of DNA-compatible reaction conditions for Suzuki and Sonogashira cross-coupling reactions and for reverse amide bond formation. Bioorganic & Medicinal Chemistry. 2021, 41, 0968-0896.
Shi, Y.; et al. DNA-encoded libraries (DELs): a review of on-DNA chemistries and their output. RSC advances. 2021, 11(4): 2359-2376.

For research use only. Not intended for any clinical use.