Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis

Man Kyu Shim, Hong Yeol Yoon, Sangmin Lee, Mun Kyeong Jo, Jooho Park, Jong Ho Kim, Seo Young Jeong, Ick Chan Kwon, Kwang Meyung Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Apoptosis is one of the most important intracellular events in living cell, which is a programmed cell death interrelated with caspase enzyme activity for maintaining homeostasis in multicellular organisms. Therefore, direct apoptosis imaging of living cells can provide enormous advantages for diagnosis, drug discovery, and therapeutic monitoring in various diseases. However, a method of direct apoptosis imaging has not been fully validated, especially for live cells in in vitro and in vivo. Herein, we developed a new apoptosis imaging technology via a direct visualization of active caspase-3/-7 activity in living cells. For this, we synthesized a caspase-3/-7-specific cleavable peptide (KGDEVD) conjugated triacetylated N-azidoacetyl-D-mannosamine (Apo-S-Ac3ManNAz), wherein the Apo-S-Ac3ManNAz can be cleaved by the active caspase-3/-7 in live apoptotic cells and the cleaved Ac3ManNAz molecules can further generate targetable azido groups (N3) on the living cell surface. Importantly, the azido groups on the apoptotic tumor cells could be visualized with Cy5.5-conjugated dibenzylcyclooctyne (DBCO-Cy5.5) via bioorthogonal click chemistry in vitro cell culture condition and in vivo tumor-bearing mice. Therefore, our Apo-S-Ac3ManNAz can be utilized for the further applications in tumor therapy as a monitoring tool for anticancer efficacy and optimization of anticancer new drugs in cell culture system and in tumor-bearing mice.

Original languageEnglish
Article number16635
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Caspase 7
Caspase 3
Apoptosis
Neoplasms
Cell Culture Techniques
Click Chemistry
Drug Discovery
Caspases
Homeostasis
Cell Death
Technology
Peptides
Enzymes
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis. / Shim, Man Kyu; Yoon, Hong Yeol; Lee, Sangmin; Jo, Mun Kyeong; Park, Jooho; Kim, Jong Ho; Jeong, Seo Young; Kwon, Ick Chan; Kim, Kwang Meyung.

In: Scientific Reports, Vol. 7, No. 1, 16635, 01.12.2017.

Research output: Contribution to journalArticle

Shim, MK, Yoon, HY, Lee, S, Jo, MK, Park, J, Kim, JH, Jeong, SY, Kwon, IC & Kim, KM 2017, 'Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis', Scientific Reports, vol. 7, no. 1, 16635. https://doi.org/10.1038/s41598-017-16653-2
Shim, Man Kyu ; Yoon, Hong Yeol ; Lee, Sangmin ; Jo, Mun Kyeong ; Park, Jooho ; Kim, Jong Ho ; Jeong, Seo Young ; Kwon, Ick Chan ; Kim, Kwang Meyung. / Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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