Trifunctional norrisolide probes for the study of Golgi vesiculation

Inspired by the effect of norrisolide on the Golgi complex, we synthesized norrisolide probes that contain: the perhydroindane core of the parent natural product for Golgi localization, a crosslinking unit (aryl azide or epoxide) for covalent binding to the target, and a tag (biotin or iodine) for subsequent target purification. We found that biotin-containing probes 14, 20 and 24 induced inefficient Golgi vesiculation. However, the iodinated probe 25 induced extensive and irreversible Golgi fragmentation. This probe can be used for the isolation of the cellular target of norrisolide.

Graphical abstractThe synthesis of norrisolide probes and their effect on the Golgi complex is presented. The studies led to the identification of probe 25, that contains a Golgi localization motif attached to a bisepoxide crosslinking unit and an iodine tag. This probe induced efficient and irreversible vesiculation of the Golgi membranes and could be used for the isolation of the cellular target of norrisolide.Figure optionsDownload full-size imageDownload as PowerPoint slide