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Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity

文献类型：期刊论文

作者Huang, Qingsheng1,2,6; Peng, Yin3; Peng, Yuefeng1,5,6; Lin, Huijuan4; Deng, Shiqi3; Feng, Shengzhong1,6; Wei, Yanjie1,6
刊名METHODS
出版日期2024-04-01
卷号224页码:35-46
关键词XIAP Apoptosis Antagonist Smac mimetic Caspase-3 Caspase-9
ISSN号1046-2023
DOI10.1016/j.ymeth.2024.02.004
英文摘要Bivalent Smac mimetics have been shown to possess binding affinity and pro-apoptotic activity similar to or more potent than that of native Smac, a protein dimer able to neutralize the anti-apoptotic activity of an inhibitor of caspase enzymes, XIAP, which endows cancer cells with resistance to anticancer drugs. We design five new bivalent Smac mimetics, which are formed by various linkers tethering two diazabicyclic cores being the IAP binding motifs. We built in silico models of the five mimetics by the TwistDock workflow and evaluated their conformational tendency, which suggests that compound 3, whose linker is n-hexylene, possess the highest binding potency among the five. After synthesis of these compounds, their ability in tumour cell growth inhibition and apoptosis induction displayed in experiments with SK-OV-3 and MDA-MB-231 cancer cell lines confirms our prediction. Among the five mimetics, compound 3 displays promising pro-apoptotic activity and deserves further optimization.
资助项目Key Research and Development Project of Guangdong Province[2021B0101310002] ; National Key Research and Development Program of China[2021YFF1200100] ; Strategic Priority CAS Project[XDB38050100] ; National Science Foundation of China[31601028] ; National Science Foundation of China[62272449] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Shenzhen Basic Research Fund[RCYX20200714114734194] ; Shenzhen Basic Research Fund[KQTD202 00820113106007] ; Youth Innovation Promotion Association[Y2021101] ; CAS ; Hanshan Normal University[QD202127]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:001205886900001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.204/handle/2XEOYT63/39914]  
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Feng, Shengzhong; Wei, Yanjie
作者单位1.Chinese Acad Sci, Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518055, Peoples R China
2.Hanshan Normal Univ, Sch Math & Stat, Chaozhou 521041, Peoples R China
3.Shenzhen Univ, Sch Med, Dept Pharmacol, Guangdong Key Lab Genome Stabil & Dis Prevent, Shenzhen 518060, Peoples R China
4.Guangdong Women & Children Hosp, Dept Ultrasound, Guangzhou 510000, Peoples R China
5.Food & Drug Adm FDA, Ctr Drug Evaluat & Res CDER, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA
6.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Intelligent Bioinformat, Shenzhen 518055, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Qingsheng,Peng, Yin,Peng, Yuefeng,et al. Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity[J]. METHODS,2024,224:35-46.
APA Huang, Qingsheng.,Peng, Yin.,Peng, Yuefeng.,Lin, Huijuan.,Deng, Shiqi.,...&Wei, Yanjie.(2024).Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity.METHODS,224,35-46.
MLA Huang, Qingsheng,et al."Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity".METHODS 224(2024):35-46.

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来源：计算技术研究所

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