The clickable activity-based probe of anti-apoptotic calenduloside E
Context: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the other ta...
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doaj-db3189fdc83b4c6f846173bbf370c6c22020-11-25T02:10:12ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162019-01-0157113313910.1080/13880209.2018.15576991557699The clickable activity-based probe of anti-apoptotic calenduloside EYu Tian0Shan Wang1Hai Shang2Wen-Qian Wang3Bao-Qi Wang4Xi Zhang5Xu-Dong Xu6Gui-Bo Sun7Xiao-Bo Sun8Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeTianjin Institute of Pharmaceutical ResearchCenter of Research and Development on Life Sciences and Environment Sciences, Harbin University of CommerceCenter of Research and Development on Life Sciences and Environment Sciences, Harbin University of CommerceInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeContext: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the other targets of CE still need to be identified with more efficient probes. Objective: This study investigates CE analogue (CEA) as one clickable activity-based probe for use in exploring anti-apoptotic CE targets. Materials and methods: Pretreatment of HUVECs with CEA (1.25 μM) for 8 hr, followed by ox-LDL stimulation for 24 h. Flow cytometry analysis and JC-1 staining assays were performed The kinetic constant measurements were tested by the Biacore T200, CM5 Sensor Chip which was activated by using sulpho-NHS/EDC. Ligands were dissolved and injected with a concentration of 12.5, 6.25, 3.125, 1.56, 0.78 and 0 μM. Results: CEA was confirmed to possess an anti-apoptotic effect. The probable targets of CE/CEA were calculated, and as one of the higher scores proteins (Fit values: 0.88/0.86), Hsp90 properly got our attention. Molecular modelling study showed that both CE and CEA could bind to Hsp90 with the similar interaction, and the docking scores (S value) were −7.61 and −7.33. SPR assay provided more evidence to prove that CEA can interact with Hsp90 with the KD value 11.7 µM. Discussion and conclusions: Our results suggest that clickable probe CEA could alleviate ox-LDL induced apoptosis by a similar mechanism of anti-apoptotic CE, and afforded the possibility of identifying additional anti-apoptotic targets of CE.http://dx.doi.org/10.1080/13880209.2018.1557699aralia elatanatural productsce analoguemolecular modellingsprhsp90 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Tian Shan Wang Hai Shang Wen-Qian Wang Bao-Qi Wang Xi Zhang Xu-Dong Xu Gui-Bo Sun Xiao-Bo Sun |
spellingShingle |
Yu Tian Shan Wang Hai Shang Wen-Qian Wang Bao-Qi Wang Xi Zhang Xu-Dong Xu Gui-Bo Sun Xiao-Bo Sun The clickable activity-based probe of anti-apoptotic calenduloside E Pharmaceutical Biology aralia elata natural products ce analogue molecular modelling spr hsp90 |
author_facet |
Yu Tian Shan Wang Hai Shang Wen-Qian Wang Bao-Qi Wang Xi Zhang Xu-Dong Xu Gui-Bo Sun Xiao-Bo Sun |
author_sort |
Yu Tian |
title |
The clickable activity-based probe of anti-apoptotic calenduloside E |
title_short |
The clickable activity-based probe of anti-apoptotic calenduloside E |
title_full |
The clickable activity-based probe of anti-apoptotic calenduloside E |
title_fullStr |
The clickable activity-based probe of anti-apoptotic calenduloside E |
title_full_unstemmed |
The clickable activity-based probe of anti-apoptotic calenduloside E |
title_sort |
clickable activity-based probe of anti-apoptotic calenduloside e |
publisher |
Taylor & Francis Group |
series |
Pharmaceutical Biology |
issn |
1388-0209 1744-5116 |
publishDate |
2019-01-01 |
description |
Context: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the other targets of CE still need to be identified with more efficient probes. Objective: This study investigates CE analogue (CEA) as one clickable activity-based probe for use in exploring anti-apoptotic CE targets. Materials and methods: Pretreatment of HUVECs with CEA (1.25 μM) for 8 hr, followed by ox-LDL stimulation for 24 h. Flow cytometry analysis and JC-1 staining assays were performed The kinetic constant measurements were tested by the Biacore T200, CM5 Sensor Chip which was activated by using sulpho-NHS/EDC. Ligands were dissolved and injected with a concentration of 12.5, 6.25, 3.125, 1.56, 0.78 and 0 μM. Results: CEA was confirmed to possess an anti-apoptotic effect. The probable targets of CE/CEA were calculated, and as one of the higher scores proteins (Fit values: 0.88/0.86), Hsp90 properly got our attention. Molecular modelling study showed that both CE and CEA could bind to Hsp90 with the similar interaction, and the docking scores (S value) were −7.61 and −7.33. SPR assay provided more evidence to prove that CEA can interact with Hsp90 with the KD value 11.7 µM. Discussion and conclusions: Our results suggest that clickable probe CEA could alleviate ox-LDL induced apoptosis by a similar mechanism of anti-apoptotic CE, and afforded the possibility of identifying additional anti-apoptotic targets of CE. |
topic |
aralia elata natural products ce analogue molecular modelling spr hsp90 |
url |
http://dx.doi.org/10.1080/13880209.2018.1557699 |
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