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

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Barth, N. D., Subiros-Funosas, R., Mendive-Tapia, L., Duffin, R., Shields, M. A., Cartwright, J. A., Henriques, S. T., Sot, J., Goñi, F. M., Lavilla, R., Marwick, J. A., Vermeren, S., Rossi, A. G., Egeblad, M., Dransfield, I., Vendrell, M. (August 2020) A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis. Nat Commun, 11 (1). p. 4027. ISSN 2041-1723

DOI: 10.1038/s41467-020-17772-7

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.

Item Type:	Paper
Additional Information:	2041-1723 Barth, Nicole D Subiros-Funosas, Ramon Mendive-Tapia, Lorena Duffin, Rodger Shields, Mario A Orcid: 0000-0002-3562-9875 Cartwright, Jennifer A Orcid: 0000-0003-1143-9011 Henriques, Sónia Troeira Sot, Jesus Goñi, Felix M Lavilla, Rodolfo Orcid: 0000-0001-9159-6089 Marwick, John A Vermeren, Sonja Orcid: 0000-0002-8460-0884 Rossi, Adriano G Egeblad, Mikala Orcid: 0000-0002-3371-1445 Dransfield, Ian Vendrell, Marc Orcid: 0000-0002-5392-9740 BB/M025160/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom P30 CA045508/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Nat Commun. 2020 Aug 12;11(1):4027. doi: 10.1038/s41467-020-17772-7.
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis Investigative techniques and equipment > imaging > flourescence bleaching
CSHL Authors:	Egeblad, Mikala Shields, Mario
Communities:	CSHL labs > Egeblad lab CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User:	Matthew Dunn
Date:	12 August 2020
Date Deposited:	02 Oct 2020 19:30
Last Modified:	26 Oct 2020 15:48
PMCID:	PMC7423924
URI:	https://repository.cshl.edu/id/eprint/39784

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