title: Fragmentation of Golgi membranes by norrisolide and designed analogues.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Brady
authors.forename: Erin K
authors.initials: EK
authors.lastname: Wallace
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Gianni
authors.initials: G
authors.lastname: Guizzunti
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
mesh_terms: 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
chemical_list: D004224:Diterpenes; C485194:norrisolide