Design and synthesis of novel photoaffinity probes for study of the target proteins of oleanolic acid

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1036-9. doi: 10.1016/j.bmcl.2011.11.123. Epub 2011 Dec 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Glycogen Phosphorylase, Muscle Form / antagonists & inhibitors*
  • Molecular Structure
  • Muscle, Skeletal / enzymology*
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology*
  • Photoaffinity Labels / chemical synthesis
  • Photoaffinity Labels / chemistry
  • Photoaffinity Labels / pharmacology*
  • Rabbits
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Photoaffinity Labels
  • Oleanolic Acid
  • Glycogen Phosphorylase, Muscle Form