Abstract
Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Herein we report the mode of action of perthamide C, a natural cyclopeptide isolated from the marine sponge Theonella swinhoei. Through an emerging mass spectrometry-based chemical proteomics approach, Heat Shock Protein 90 and Glucose Regulated Protein 94 were identified as key targets of perthamide C and this evidence has been validated using surface plasmon resonance. The ability of perthamide C to influence heat shock protein-mediated cell apoptosis revealed that this marine metabolite could be a good candidate for the development of a lead compound with therapeutic applications based on apoptosis modulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Aquatic Organisms / chemistry*
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Benzoquinones / pharmacology
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Cell Line
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Chromatography, Affinity
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Cisplatin / pharmacology
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Docetaxel
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HSP70 Heat-Shock Proteins / metabolism
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HSP90 Heat-Shock Proteins / metabolism*
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Hep G2 Cells
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Humans
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Immobilized Proteins / pharmacology
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Lactams, Macrocyclic / pharmacology
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Membrane Proteins / metabolism
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Mice
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Microspheres
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Protective Agents / pharmacology
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Protein Binding / drug effects
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Surface Plasmon Resonance
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Taxoids / pharmacology
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Theonella / chemistry
Substances
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Benzoquinones
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HSP70 Heat-Shock Proteins
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HSP90 Heat-Shock Proteins
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Immobilized Proteins
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Lactams, Macrocyclic
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Membrane Proteins
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Peptides, Cyclic
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Protective Agents
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Taxoids
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glucose-regulated proteins
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perthamide C
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Docetaxel
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tanespimycin
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Cisplatin