Following the Lead from Nature with Covalent Inhibitors

Authors

  • Roman Lagoutte Faculty of Science, Department of Organic Chemistry NCCR Chemical Biology University of Geneva 30 quai Ernest Ansermet, CH-1205 Geneva, Switzerland
  • Nicolas Winssinger Faculty of Science, Department of Organic Chemistry NCCR Chemical Biology University of Geneva 30 quai Ernest Ansermet, CH-1205 Geneva, Switzerland. nicolas.winssinger@unige.com

DOI:

https://doi.org/10.2533/chimia.2017.703

Keywords:

Covalent inhibitors, Mode of action, Natural products, Protein modification, Target identification

Abstract

Covalent inhibitors are re-emerging as pharmacologically interesting entities with several candidates having received recent approval for therapeutic intervention. Nature has embraced this strategy and many natural products possess mildly electrophilic moieties able to covalently engage a target protein. This review surveys recent case studies for the identification of the target proteins of natural products. While sesquiterpene lactones represent a vast repertoire of covalent inhibitors, they can also be found in other classes of natural products, with sometimes unusual mechanisms to unmask the electrophilic moieties. These examples ought to be inspiring for the development of new biochemical probes and tomorrow's first-in-class drugs.

Downloads

Published

2017-10-25

Issue

Section

Scientific Articles