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The synthesis and characterization of a novel DNA-encoded library of macrocyclic peptide derivatives are described; the macrocycles are based on three sets of proteinogenic and non-proteinogenic amino acid building blocks and featuring the use of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction for ring closure. The library (termed YO-DEL) which contains 1 254 838 compounds, was encoded with DNA in single-stranded format and was screened against target proteins of interest using affinity capture procedures and photocrosslinking. YO-DEL selections yielded specific binders against serum albumins, carbonic anhydrases and NKp46, a marker of activated Natural Killer cells. © 2021 Wiley-VCH GmbH.


Yuichi Onda, Gabriele Bassi, Abdullah Elsayed, Franziska Ulrich, Sebastian Oehler, Louise Plais, Jörg Scheuermann, Dario Neri. A DNA-Encoded Chemical Library Based on Peptide Macrocycles. Chemistry (Weinheim an der Bergstrasse, Germany). 2021 Apr 26;27(24):7160-7167

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PMID: 33586277

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