Chemical biology studies on norrisolide.
The cellular activity of norrisolide (7), a novel Golgi-vesiculating agent, was dissected as function of its chemical structure. This natural product induces irreversible vesiculation of the Golgi membranes and blocks protein transport at the level of the Golgi. The Golgi localization and fragmentation effects of 7 depend on the presence of the perhydroindane core, while the irreversibility of fragmentation depends on the acetyl group of 7. We show that fluorescent derivatives of norrisolide are able to localize to the Golgi apparatus and represent important tools for the study of the Golgi structure and function.
Guizzunti
Gianni
G
Department of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Brady
Thomas P
TP
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Fischer
Derek
D
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Malhotra
Vivek
V
Department of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Theodorakis
Emmanuel A
EA
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
D000818:Animals; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D015394:Molecular Structure; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004224:Diterpenes; D008565:Membrane Proteins; C485194:norrisolide