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

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

机构地区：[1]Program in Chemical Biology,Department of Chemical Physiology and Biochemistry,Oregon Health&Science University,Portland,OR 97239,USA [2]Proteomics Shared Resource,Oregon Health&Science University,Portland,OR 97239,USA [3]Knight Cancer Institute,Oregon Health&Science University,Portland,OR 97239,USA [4]Department of Neurology,Oregon Health&Science University,Portland,OR 97239,USA

出　　处：《Acta Pharmaceutica Sinica B》2022年第5期2406-2416,共11页药学学报（英文版）

基　　金：partially by the financial supports from the National Institutes of Health R01 CA197513 (XX),R01GM122820 (XX) and R21EB028425 (BXL),USA;performed by the OHSU Proteomics Shared Resource with partial support from NIH core grants P30EY010572,P30CA069533,and S10RR025571,USA。

摘　　要：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.

关 键 词：Betulinic acid CANCER DIAZIRINE Natural product Photoaffinity probe TROPOMYOSIN 

分 类 号：R284[医药卫生—中药学]