Nature Communications (Jun 2021)

RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site

  • Katarzyna Z. Haza,
  • Heather L. Martin,
  • Ajinkya Rao,
  • Amy L. Turner,
  • Sophie E. Saunders,
  • Britta Petersen,
  • Christian Tiede,
  • Kevin Tipping,
  • Anna A. Tang,
  • Modupe Ajayi,
  • Thomas Taylor,
  • Maia Harvey,
  • Keri M. Fishwick,
  • Thomas L. Adams,
  • Thembaninkosi G. Gaule,
  • Chi H. Trinh,
  • Matthew Johnson,
  • Alexander L. Breeze,
  • Thomas A. Edwards,
  • Michael J. McPherson,
  • Darren C. Tomlinson

DOI
https://doi.org/10.1038/s41467-021-24316-0
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

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Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores.