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

Medientyp: E-Artikel
Titel: A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis
Beteiligte: Barth, Nicole D.; Subiros-Funosas, Ramon; Mendive-Tapia, Lorena; Duffin, Rodger; Shields, Mario A.; Cartwright, Jennifer A.; Henriques, Sónia Troeira; Sot, Jesus; Goñi, Felix M.; Lavilla, Rodolfo; Marwick, John A.; Vermeren, Sonja; Rossi, Adriano G.; Egeblad, Mikala; Dransfield, Ian; Vendrell, Marc
Erschienen: Springer Science and Business Media LLC, 2020
Erschienen in: Nature Communications
Sprache: Englisch
DOI: 10.1038/s41467-020-17772-7
ISSN: 2041-1723
Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>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<jats:bold>Apo-15</jats:bold>) 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<jats:bold>Apo-15</jats:bold>. We demonstrate that<jats:bold>Apo-15</jats:bold>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.</jats:p>
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