Rationally Designed Amanitins Achieve Enhanced Cytotoxicity

  • J Med Chem. 2022 Aug 11;65(15):10357-10376. doi: 10.1021/acs.jmedchem.1c02226.
Mihajlo Todorovic  1 ,  Paul Rivollier  1 ,  Antonio A W L Wong  1 ,  Zhou Wang  1 ,  Alla Pryyma  1 ,  Tuan Trung Nguyen  1 ,  Kayla C Newell  1 ,  Juliette Froelich  1 ,  David M Perrin  1
Affiliations
  • 1. Chemistry Department, 2036 Main Mall, The University of British Columbia, 2036 Main Mall, Vancouver, BC V6T-1Z1, Canada.
PMID: 35696491 DOI: 10.1021/acs.jmedchem.1c02226
Abstract

For 70 years, α-amanitin, the most cytotoxic peptide in its class, has been without a synthetic rival; through synthesis, we address the structure-activity relationships to inform the design of new amatoxins and disclose analogues that are more cytotoxic than the natural product when evaluated on CHO, HEK293, and HeLa cells, whereas on liver-derived HepG2 cells, the same toxins show diminished cytotoxicity.

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