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DNA-Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution
Millicent Dockerill1, Nicolas Winssinger1
1Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Sciences, University of Geneva, 1211, Geneva, Switzerland.
Angewandte Chemie (International Ed. in English)
|December 2, 2022
Summary
DNA-encoded libraries (DEL) accelerate drug discovery by enabling massive screening. This review covers technologies that translate DNA tags into synthetic molecules, harnessing evolutionary principles for molecular evolution.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Drug Discovery
Background:
- DNA-encoded library (DEL) technology offers a powerful platform for identifying drug ligands at scale.
- DEL platforms utilize vast libraries, significantly exceeding traditional high-throughput screening capacities.
- Current DEL applications often use DNA tags as barcodes, limiting direct linkage to synthetic products.
Purpose of the Study:
- To review technologies enabling the "translation" of DNA tags into their linked synthetic molecules.
- To explore the application of these translation technologies in harnessing Darwinian evolutionary pressure.
- To highlight advancements in DEL for accelerated and large-scale ligand identification.
Main Methods:
- Biochemical methods for DNA tag to molecule translation.
- Chemical methods for DNA tag to molecule translation.
- Review of existing literature and technologies in the DEL field.
Main Results:
- Technologies for both biochemical and chemical translation of DNA tags are emerging.
- These translation capabilities allow for the exploitation of genotype-phenotype connections.
- The reviewed technologies enable the application of evolutionary principles to molecular discovery.
Conclusions:
- Advancements in DEL "translation" technologies are crucial for realizing the full potential of DNA-encoded libraries.
- Harnessing evolutionary pressure through DEL translation can significantly enhance drug discovery efficiency.
- The field is moving towards more integrated DEL systems where DNA tags provide direct synthetic information.
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