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

Nicole D. Barth, Ramon Subiros-Funosas, Lorena Mendive-Tapia, Rodger Duffin, Mario A. Shields, Jennifer A. Cartwright, Sónia Troeira Henriques, Jesus Sot, Felix M. Goñi, Rodolfo Lavilla, John A. Marwick, Sonja Vermeren, Adriano G. Rossi, Mikala Egeblad, Ian Dransfield () and Marc Vendrell ()
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Nicole D. Barth: University of Edinburgh
Ramon Subiros-Funosas: University of Edinburgh
Lorena Mendive-Tapia: University of Edinburgh
Rodger Duffin: University of Edinburgh
Mario A. Shields: Cold Spring Harbor Laboratory
Jennifer A. Cartwright: University of Edinburgh
Sónia Troeira Henriques: The University of Queensland
Jesus Sot: Universidad del País Vasco
Felix M. Goñi: Universidad del País Vasco
Rodolfo Lavilla: University of Barcelona
John A. Marwick: University of Edinburgh
Sonja Vermeren: University of Edinburgh
Adriano G. Rossi: University of Edinburgh
Mikala Egeblad: Cold Spring Harbor Laboratory
Ian Dransfield: University of Edinburgh
Marc Vendrell: University of Edinburgh

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17772-7

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DOI: 10.1038/s41467-020-17772-7

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