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Title: A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis
Author: Barth, Nicole D.
Subirós Funosas, Ramon
Mendive Tapia, Lorena
Duffin, Rodger
Shields, Mario A.
Cartwright, Jennifer A.
Troeira Henriques, Sónia
Sot, Jesus
Goñi, Felix M.
Lavilla Grífols, Rodolfo
Marwick, John A.
Vermeren, Sonja
Rossi, Adriano G.
Egeblad, Mikala
Dransfield, Ian
Vendrell, Marc
Keywords: Pèptids
Amino acids
Issue Date: 12-Aug-2020
Publisher: Nature Publishing Group
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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It is part of: Nature Communications, 2020, vol. 11, p. 1-14
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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