title: Probing the anticancer mechanism of (-)-ainsliatrimer A through diverted total synthesis and bioorthogonal ligation.
abstract: Herein, we report an efficient approach for exploring the novel anticancer mechanism of (-)-ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by pretarget imaging revealed that PPARγ, a nucleus receptor, was a functional cellular target of ainsliatrimer A. We also confirmed that the anticancer activity of ainsliatrimer A was caused by the activation of PPARγ.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871 (China) http://www.chem.pku.edu.cn/leigroup/
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Dong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists; D012717:Sesquiterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D047495:PPAR gamma; D012717:Sesquiterpenes; C530462:ainsliadimer A
keywords: antitumor agents; bioorganic chemistry; bioorthogonal ligation; diverted total synthesis; target identification