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, Marc Vendrell

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number4027
JournalNature Communications
Publication statusPublished - 12 Aug 2020


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