Exploring the mode of action of ipomoeassin natural glycoresins.

by Hu, Zhijian; Zong, Guanghui; Aljewari, Hazim; Zhou, Jianhong; Du, Yuchun; Shi, Wei

Ipomoeassin F is a representative member of a resin glycoside family that showed potent cell growth inhibition activity but with an unknown mode of action. Recently, we finished the total synthesis of ipomoeassin F through a more efficient route and gained better understanding of its pharmacophore. Based on the previous work, several fluorescent derivs. and functional probes of ipomoeassin F were designed and prepd. for cell imaging and target identification studies. Using a confocal microscope, it was revealed that ipomoeassin F is largely localized in endoplasmic reticulum (ER), which matches the preliminary data we obtained through SILAC-based quant. proteomics. In addn., activity-based protein profiling is being used to verify whether ipomoeassins are covalent protein-modifiers or not. All these initial results will greatly facilitate future efforts to develop ipomoeassins as therapeutic/preventative agents or as chem. probes for basic biomedical research.