Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 18, Issue 25, Pages 7729-7737Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201200952
Keywords
DNA-encoded chemical libraries; drug discovery; high-throughput screening; inhibitors; ligands
Categories
Funding
- ETH Zurich
- Swiss National Science Foundation
- Philochem AG
- KTI [8868.1 PFDS-LS]
- Swiss Bridge Foundation
- Stammbach Foundation
- Gebert Ruf Foundation
Ask authors/readers for more resources
Libraries of chemical compounds individually coupled to encoding DNA tags (DNA-encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high-quality DNA-encoded chemical library comprising 30?000 drug-like compounds; this was screened in 170 different affinity capture experiments. High-throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor-associated antigen carbonic anhydrase IX (CA IX) and the pro-inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL-2 was confirmed by molecular docking. Our findings suggest that DNA-encoded chemical libraries allow the facile identification of drug-like ligands principally to any protein of choice, including molecules capable of disrupting high-affinity proteinprotein interactions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available