1. Academic Validation
  2. A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

  • Nat Commun. 2020 Aug 12;11(1):4027. doi: 10.1038/s41467-020-17772-7.
Nicole D Barth # 1 Ramon Subiros-Funosas # 1 Lorena Mendive-Tapia 1 Rodger Duffin 1 Mario A Shields 2 Jennifer A Cartwright 1 Sónia Troeira Henriques 3 4 Jesus Sot 5 Felix M Goñi 5 Rodolfo Lavilla 6 John A Marwick 1 Sonja Vermeren 1 Adriano G Rossi 1 Mikala Egeblad 2 Ian Dransfield 7 Marc Vendrell 8
Affiliations

Affiliations

  • 1 Centre for Inflammation Research, University of Edinburgh, EH16 4TJ, Edinburgh, UK.
  • 2 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
  • 3 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
  • 4 School of Biomedical Sciences, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, 4102, Australia.
  • 5 Instituto Biofisika (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, Campus de Leioa, 48940, Leioa, Spain.
  • 6 Laboratory of Medicinal Chemistry and Institute of Biomedicine U. Barcelona (IBUB), Faculty of Pharmacy, University of Barcelona, 08028, Barcelona, Spain.
  • 7 Centre for Inflammation Research, University of Edinburgh, EH16 4TJ, Edinburgh, UK. i.dransfield@ed.ac.uk.
  • 8 Centre for Inflammation Research, University of Edinburgh, EH16 4TJ, Edinburgh, UK. marc.vendrell@ed.ac.uk.
  • # Contributed equally.
Abstract

Programmed cell death or Apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and Cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced Apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics.

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