Synthesis and mode of action of oligomeric sesquiterpene lactones.
Covering: up to 2015In this highlight we describe two case studies from our laboratory, involving the biomimetic syntheses and the biological mechanism elucidation of the bioactive oligomeric sesquiterpenoids, (+)-ainsliadimer A () and (-)-ainsliatrimer A (). Ainsliadimer A possesses potent anti-inflammatory activity by inhibition of the NF-κB signalling pathway via binding at a previously untargeted allosteric site. (-)-Ainsliatrimer A induces apoptosis in cancer cells by activation of PPARγ. Furthermore, we highlight a new bioorthogonal ligation (TQ-ligation) developed in our laboratory which facilitates the target identification of complex natural products via pre-target fluorescence imaging and affinity chromatography. Generally, this paper will discuss the complete process from total synthesis to biological studies of complex natural products, and from the establishment of new bio-orthogonal chemistry to successful target identification. Our approach provides a systematic and efficient methodology for addressing the challenge of natural product target identification.
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. xglei@pku.edu.cn.
Chao
C
Li
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. xglei@pku.edu.cn.
Alexander X
AX
Jones
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. xglei@pku.edu.cn and National Institute of Biological Sciences (NIBS), Beijing 102206, China.
Xiaoguang
X
Lei
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes