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CORDIS

Drug Discovery using DNA-encoded Chemistry

Objective

DNA-encoded based selection methods represent a novel avenue for the facile discovery of binding molecules from large libraries. Unique DNA fragments covalently attached to small molecules serve as amplifiable identification barcodes. The encoding allows the in vitro selection of ligands at sub‐picomolar concentrations from large library populations by affinity capture on a target protein of interest, in analogy to established technologies for the selection of binding polypeptides (e.g. antibodies). Libraries before and after selection are characterized by PCR amplification of the DNA codes and relative quantification of library members is then acquired using high‐throughput sequencing. The most enriched compounds can then be further analyzed in biological assays, in the presence or in the absence of linked DNA. While most libraries to date have been assembled using amide bond forming reactions, we will explore the use of bioorthogonal, metal free click reactions such as the thiol-ene reaction for the efficient construction of DNA-encoded libraries. This will enable the identification of novel small organic molecules capable of binding specifically to biological and pharmacologically relevant protein targets.

Call for proposal

FP7-PEOPLE-2010-IEF
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Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
EU contribution
€ 186 028,80
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Agatha Keller (Prof.)
Links
Total cost
No data