Institute of Traditional Chinese Medicine, Chengde Medical College, Chengde 067000, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1036-9. doi: 10.1016/j.bmcl.2011.11.123. Epub 2011 Dec 7.
To explore the molecular mechanisms of oleanolic acid, two novel photoaffinity probes were synthesized based on the structure-activity relationship reported previously. Their potency were evaluated in an enzyme inhibition assay against rabbit muscle glycogen phosphorylase a (RMGPa), a known target protein of oleanolic acid. The inhibitory activity of probe 2 was only about two-fold less potent than the mother compound oleanolic acid. The photoaffinity labeling experiments were also performed and two proteins were specifically tagged by probe 2. The results suggest that the synthesized probes could be used as powerful tools to isolate and identify the target proteins of oleanolic acid.
为了探索齐墩果酸的分子机制，根据先前报道的结构-活性关系，我们合成了两种新型的光亲和探针。在对兔肌肉糖原磷酸化酶 a（RMGPa）的酶抑制测定中评估了它们的效力，RMGPa 是齐墩果酸的已知靶蛋白。探针 2 的抑制活性仅比母体化合物齐墩果酸低约两倍。还进行了光亲和标记实验，探针 2 特异性标记了两种蛋白质。结果表明，合成的探针可用作分离和鉴定齐墩果酸靶蛋白的有力工具。
