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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-10, Vol.14 (20), p.5035-5039
Main Authors: BRADY, Thomas P, WALLACE, Erin K, SUN HEE KIM, GUIZZUNTI, Gianni, MALHOTRA, Vivek, THEODORAKIS, Emmanuel A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell structures and functions
Cells, Cultured
Diterpenes - chemistry
Diterpenes - pharmacology
Fundamental and applied biological sciences. Psychology
Golgi apparatus
Golgi Apparatus - drug effects
Golgi Apparatus - ultrastructure
Intracellular Membranes - drug effects
Intracellular Membranes - ultrastructure
Kidney - ultrastructure
Molecular and cellular biology
Rats
Structure-Activity Relationship
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.08.003