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

doi:10.1016/j.ymeth.2024.02.004

	Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity
	Huang, Qingsheng 1,2,3; Peng, Yin 4; Peng, Yuefeng 1,2,6; Lin, Huijuan 5; Deng, Shiqi 4; Feng, Shengzhong 1,2; Wei, Yanjie 1,2
	2024-04-01
发表期刊	METHODS
ISSN	1046-2023
卷号	224 页码:35-46
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.
关键词	XIAP Apoptosis Antagonist Smac mimetic Caspase-3 Caspase-9
DOI	10.1016/j.ymeth.2024.02.004
收录类别	SCI
语种	英语
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
WOS类目	Biochemical Research Methods ; Biochemistry & Molecular Biology
WOS记录号	WOS:001205886900001
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/39915
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, Shenzhen Key Lab Intelligent Bioinformat, Shenzhen 518055, Peoples R China 2.Chinese Acad Sci, Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518055, Peoples R China 3.Hanshan Normal Univ, Sch Math & Stat, Chaozhou 521041, Peoples R China 4.Shenzhen Univ, Sch Med, Dept Pharmacol, Guangdong Key Lab Genome Stabil & Dis Prevent, Shenzhen 518060, Peoples R China 5.Guangdong Women & Children Hosp, Dept Ultrasound, Guangzhou 510000, Peoples R China 6.Food & Drug Adm FDA, Ctr Drug Evaluat & Res CDER, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA
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.