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Updated: Jul 25, 2025
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Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
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Macrocyclizing DNA-Linked Peptides via Three-Component Cyclization and Photoinduced Chemistry
Yandan Bao1,2, Minyan Xing3, Naylor Matthew4
1School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
Organic Letters
|June 29, 2023
Summary
Researchers developed new on-DNA methods for creating macrocyclic libraries, crucial for DNA-encoded library technology. These efficient techniques ensure high cyclization and DNA integrity, enabling the discovery of novel drug scaffolds.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Biotechnology
Background:
- DNA-encoded library (DEL) technology is a powerful tool for identifying hit compounds.
- Efficient on-DNA macrocyclization methods are essential for constructing DELs with high cyclization and DNA integrity.
Purpose of the Study:
- To develop and report novel on-DNA methodologies for macrocyclic library construction.
- To ensure high cyclization efficiency and maintain DNA integrity during the process.
Main Methods:
- Utilized OPA-mediated three-component cyclization reactions.
- Employed native amino acid handles for on-DNA reactions.
- Incorporated photoredox chemistries for macrocyclization.
Main Results:
- Developed a set of efficient on-DNA macrocyclization methodologies.
- Achieved smooth reaction progression under mild conditions.
- Demonstrated good to excellent conversion rates.
- Successfully generated novel isoindole, isoindoline, indazolone, and bicyclic scaffolds.
Conclusions:
- The reported on-DNA methodologies are effective for constructing diverse macrocyclic libraries.
- These methods are compatible with DNA-encoded library technology, enhancing its capabilities.
- The generated novel scaffolds hold potential for drug discovery efforts.
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