Discovery of Protein-Protein Interaction Inhibitors by Integrating Protein Engineering and Chemical Screening Platforms

Timurs Maculins, Javier Garcia-Pardo, Anamarija Skenderovic, Jakob Gebel, Mateusz Putyrski, Andrew Vorobyov, Philipp Busse, Gabor Varga, Maria Kuzikov, Andrea Zaliani, Simin Rahighi, Veronique Schaeffer, Michael J. Parnham, Sachdev S. Sidhu, Andreas Ernst, Volker Dötsch, Masato Akutsu, Ivan Dikic

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Maculins et al. describe an approach for identifying small molecule inhibitors of protein-protein interactions that are considered “hard to target.” The team engineered high-affinity variants of one interacting partner that enabled robust chemical screening. Top hits identified using this approach inhibited cellular signaling driven by the endogenous interaction.

Original languageEnglish
Pages (from-to)1441-1451.e7
JournalCell Chemical Biology
Volume27
Issue number11
DOIs
Publication statusPublished - 2020 Nov 19
Externally publishedYes

Keywords

  • LUBAC
  • NF-κB
  • cellular screening
  • high throughput
  • hit identification
  • inhibitor
  • protein engineering
  • protein-protein interaction
  • small molecule
  • ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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