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.
Nat Prod Rep. 2016 May 4;33(5):602-11. doi: 10.1039/c5np00089k.
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.
截至 2015 年
在本篇亮点中，我们描述了来自我们实验室的两个案例研究，涉及生物模拟合成和生物活性低聚倍半萜的生物机制阐明，（+）-ainsliadimer A（）和（-）-ainsliatrimer A（）。Ainsliadimer A 通过结合以前未靶向的变构位点抑制 NF-κB 信号通路，具有强大的抗炎活性。（-）-Ainsliatrimer A 通过激活 PPARγ 在癌细胞中诱导细胞凋亡。此外，我们强调了我们实验室开发的一种新的生物正交连接（TQ 连接），它通过预靶向荧光成像和亲和层析促进了复杂天然产物的靶标鉴定。总的来说，本文将讨论从复杂天然产物的全合成到生物研究，从新的生物正交化学的建立到成功的靶标鉴定的完整过程。我们的方法为解决天然产物靶标鉴定的挑战提供了一种系统和有效的方法。
