A clickable photoaffinity probe of betulinic acid identifies tropomyosin as a target

Pedro Martín-Acosta, Qianli Meng, John Klimek, Ashok P. Reddy, Larry David, Stefanie Kaech Petrie, Bingbing X. Li, Xiangshu Xiao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.

Original languageEnglish (US)
Pages (from-to)2406-2416
Number of pages11
JournalActa Pharmaceutica Sinica B
Volume12
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • Betulinic acid
  • Cancer
  • Diazirine
  • Natural product
  • Photoaffinity probe
  • Tropomyosin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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