Design and synthesis of novel photoaffinity probes for study of the target proteins of oleanolic acid.
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.
Institute of Traditional Chinese Medicine, Chengde Medical College, Chengde 067000, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Liying
L
Zhang
Yingxia
Y
Zhang
Jizhe
J
Dong
Jun
J
Liu
Luyong
L
Zhang
Hongbin
H
Sun
D000818:Animals; D004305:Dose-Response Relationship, Drug; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000201:enzymology*; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019920:Photoaffinity Labels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D019920:Photoaffinity Labels; D009828:Oleanolic Acid; D024982:Glycogen Phosphorylase, Muscle Form