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A versatile and Lipinski-compliant DNA-encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB-DEL library, constructed in single-stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single-stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self-assembled selectable chemical structures, leading to the identification of affinity-matured compounds.

Original publication

DOI

10.1002/advs.202001970

Type

Journal article

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Publication Date

11/2020

Volume

7

Addresses

Department of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 Switzerland.