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Cover Feature: Activity‐Directed Synthesis of Inhibitors of the p53/ h DM2 Protein–Protein Interaction (Chem. Eur. J. 47/2020)
Author(s) -
Green Adam I.,
Hobor Fruzsina,
Tinworth Christopher P.,
Warriner Stuart,
Wilson Andrew J.,
Nelson Adam
Publication year - 2020
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.202003334
Subject(s) - function (biology) , protein–protein interaction , cover (algebra) , microscale chemistry , combinatorial chemistry , chemistry , protein function , computational biology , scaffold protein , stereochemistry , biochemistry , biology , microbiology and biotechnology , signal transduction , mechanical engineering , mathematics education , mathematics , gene , engineering
Activity‐directed synthesis was harnessed in the function‐driven discovery of inhibitors of a protein–protein interaction. Pairs of substrates, inspired by known ligands, were exploited in 346 microscale reactions. The crude reaction mixtures were screened for biological function, and the products of promising reactions purified and characterised. Four novel and distinct inhibitor series were discovered. The artwork illustrates how motifs found in known ligands were incorporated into substrates, ultimately enabling scaffold‐hopping to new inhibitor series. More information can be found in the Communication by A. Nelson et al. on page 10682.