The clickable activity-based probe of anti-apoptotic calenduloside E

Pharmaceutical Biology

Bao-Qi Wang¹  Xi Zhang¹  Xu-Dong Xu²  Shan Wang²  Xiao-Bo Sun²  Hai Shang²  Yu Tian²  Gui-Bo Sun²  Wen-Qian Wang³ 

[1] Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce;Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College;Tianjin Institute of Pharmaceutical Research;

关键词: aralia elata;    natural products;    ce analogue;    molecular modelling;    spr;    hsp90;   

DOI  :  10.1080/13880209.2018.1557699

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown