Fragmentation of Golgi membranes by norrisolide and designed analogues.

The effect of norrisolide (4) and designed analogues on the Golgi membranes is presented. We found that 4 is the first compound known to induce an irreversible vesiculation of these membranes. To investigate the chemical origins of this new effect we synthesized and evaluated a series of norrisolide analogues in which the chemical functionalities present in the parent structure were altered. Such structure/function studies suggest that the perhydroindane core of 4 is critical for binding to the target protein, while the C21 acetate unit is essential for the irreversible vesiculation of the Golgi membranes.