Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis
- Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis
- 권익찬; 김광명; 박주호; 윤홍열; 심만규; 이상민; 조문경; 김종호; 정서영
- Issue Date
- Scientific Reports
- VOL 7, NO 16635-15
- 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.
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