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.
Brady
Thomas P
TP
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Wallace
Erin K
EK
Kim
Sun Hee
SH
Guizzunti
Gianni
G
Malhotra
Vivek
V
Theodorakis
Emmanuel A
EA
D000818:Animals; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000187:drug effects* / Q000648:ultrastructure; D007668:Kidney / Q000648:ultrastructure; D051381:Rats; D013329:Structure-Activity Relationship
D004224:Diterpenes; C485194:norrisolide