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Related Experiment Video

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Design and Synthesis of a Reconfigurable DNA Accordion Rack

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Published on: August 15, 2018

Reversible Covalent Headpiece Enables Interconversion between Double- and Single-Stranded DNA-Encoded Chemical

Guixian Zhao¹, Shuting Zhong¹, Gong Zhang^1,2

¹Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, P. R. China.

Angewandte Chemie (International Ed. in English)

|December 14, 2021

Summary

A novel reversible covalent headpiece (RCHP) enables DNA-encoded library (DEL) technology to switch between double- and single-stranded formats. This versatile RCHP method enhances DEL synthesis and applications, including novel ligand isolation.

Keywords:

DNA DNA-encoded library Drug discovery Photo-crosslinking Selection

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Published on: November 25, 2015

Area of Science:

Biochemistry
Organic Chemistry
Molecular Biology

Background:

DNA-encoded library (DEL) technology is crucial for drug discovery and chemical biology.
Current DEL methods predominantly use double-stranded DNA encoding, which limits versatility.
Single-stranded DNA formats offer greater application flexibility but are less robust for synthesis.

Purpose of the Study:

To develop a novel encoding method for DEL technology that combines robustness and versatility.
To enable reversible switching between double- and single-stranded DNA formats within DEL construction.
To expand the applicability of DEL technology in diverse experimental setups.

Main Methods:

Introduction of a "reversible covalent headpiece" (RCHP) into the DEL encoding strategy.
Demonstration of reversible interconversion between double- and single-stranded DNA formats.
Validation using encoded self-assembled chemical libraries and DNA-encoded dynamic library technology.

Main Results:

The RCHP method allows for robust synthesis of DELs.
The RCHP enables versatile applications in both double- and single-stranded DNA formats.
A novel "ternary covalent complex" methodology for ligand isolation from non-immobilized targets was developed based on RCHP.

Conclusions:

The RCHP encoding method significantly enhances the versatility and robustness of DEL technology.
This approach broadens the scope of DEL applications, including advanced ligand discovery.
The RCHP facilitates innovative methodologies like ternary covalent complex formation for target-based screening.