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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Autores principales:	Yu Tian, Shan Wang, Hai Shang, Wen-Qian Wang, Bao-Qi Wang, Xi Zhang, Xu-Dong Xu, Gui-Bo Sun, Xiao-Bo Sun
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	aralia elata natural products ce analogue molecular modelling spr hsp90 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/db3189fdc83b4c6f846173bbf370c6c2
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spelling	oai:doaj.org-article:db3189fdc83b4c6f846173bbf370c6c22021-11-17T14:21:55ZThe clickable activity-based probe of anti-apoptotic calenduloside E1388-02091744-511610.1080/13880209.2018.1557699https://doaj.org/article/db3189fdc83b4c6f846173bbf370c6c22019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2018.1557699https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: 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.Yu TianShan WangHai ShangWen-Qian WangBao-Qi WangXi ZhangXu-Dong XuGui-Bo SunXiao-Bo SunTaylor & Francis Grouparticlearalia elatanatural productsce analoguemolecular modellingsprhsp90Therapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 133-139 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	aralia elata natural products ce analogue molecular modelling spr hsp90 Therapeutics. Pharmacology RM1-950
spellingShingle	aralia elata natural products ce analogue molecular modelling spr hsp90 Therapeutics. Pharmacology RM1-950 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
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.
format	article
author	Yu Tian Shan Wang Hai Shang Wen-Qian Wang Bao-Qi Wang Xi Zhang Xu-Dong Xu Gui-Bo Sun Xiao-Bo Sun
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
publishDate	2019
url	https://doaj.org/article/db3189fdc83b4c6f846173bbf370c6c2
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The clickable activity-based probe of anti-apoptotic calenduloside E

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