Drug discovery with DNA-encoded chemical libraries
Fabian Buller1, Luca Mannocci, Jörg Scheuermann
1Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, and Philochem AG, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Bioconjugate Chemistry
|August 5, 2010
Summary
DNA-encoded chemical libraries offer a powerful method for discovering small molecule ligands. This technique uses DNA tags for selection and identification, accelerating drug discovery programs.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Biotechnology
Background:
- DNA-encoded chemical libraries (DELs) enable efficient small molecule ligand discovery.
- DELs link small molecules to DNA barcodes for identification and selection.
Purpose of the Study:
- To review experimental strategies for constructing DELs.
- To highlight selection, decoding, and hit validation technologies in drug discovery.
Main Methods:
- Library construction with millions of DNA-encoded compounds.
- In vitro affinity selection using target proteins.
- PCR amplification and high-throughput sequencing for DNA code decoding.
- Biological assays for hit validation.
Main Results:
- DELs allow selection of ligands at subpicomolar concentrations.
- High-throughput sequencing enables relative quantification of library members.
- Enriched compounds are validated in biological assays.
Conclusions:
- DELs provide a facile and efficient approach for drug discovery.
- Integrated selection, decoding, and validation strategies are crucial for successful programs.
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