Streptomyces metabolite

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Streptomyces metabolite inhibits cell
proliferation lactone active acid
inactive possible covalent modifier
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Synthesis and Reactivity of Labeled Lactacystin
Single protein target
Science, 268, 726 (1995)
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Lactacystin Binding to an N-Terminal Thr
catalytically active residue
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Velcade Bortezomib for treatment of multiple
myeloma
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Fumagillin A naturally occurring anti-angiogenic
compound
PNAS, 94, 6099 (1997)
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Biotin-Avidin Complex
KD 10-27
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Detection of Biotinylated Proteins
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Labeling the Molecular Target in Human
Endothelial Cells
Met-AP2
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Fumagillin A naturally occurring anti-angiogenic
compound
PNAS, 94, 6099 (1997)
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The 5-Lipoxygenase Pathway of Arachidonate
Metabolism
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How does one identify the target(s) of
non-covalent association?
MK-886 inhibits 5-lipoxygenase and
leukotriene biosynthesis in intact cells MK-886
does not inhibit 5-LO cell-free extracts It
prevents 5-LO translocation to nuclear membrane
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Photoaffinity Labeling of 18 Kda Protein in
Neutrophils
Nature, 343, 278 (1990)
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Inhibition of Photoaffinity Labeling
IC50 100 nM for LT biosynthesis
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Copper-Catalyzed Click Chemistry
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Science,287, 2007 (2000)
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JACS, 125, 8130 (2003)
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Specificity of Labeling
Yeast Extract