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A DNA‐Encoded Chemical Library Based on Peptide Macrocycles
Author(s) -
Onda Yuichi,
Bassi Gabriele,
Elsayed Abdullah,
Ulrich Franziska,
Oehler Sebastian,
Plais Louise,
Scheuermann Jörg,
Neri Dario
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202005423
Subject(s) - dna , cycloaddition , peptide , combinatorial chemistry , click chemistry , azide , chemistry , amino acid , alkyne , ring (chemistry) , stereochemistry , biochemistry , organic chemistry , catalysis
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.