Heat shock proteins as key biological targets of the marine natural cyclopeptide perthamide C.
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.
Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, via Ponte don Melillo, 84084 Fisciano, Italy.
Luigi
L
Margarucci
Maria Chiara
MC
Monti
Andrea
A
Mencarelli
Chiara
C
Cassiano
Stefano
S
Fiorucci
Raffaele
R
Riccio
Angela
A
Zampella
Agostino
A
Casapullo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059001:Aquatic Organisms / Q000737:chemistry*; D016227:Benzoquinones / Q000494:pharmacology; D002460:Cell Line; D002846:Chromatography, Affinity; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020349:Surface Plasmon Resonance; D043823:Taxoids / Q000494:pharmacology; D047232:Theonella / Q000737:chemistry
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D055767:Immobilized Proteins; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D020011:Protective Agents; D043823:Taxoids; C018551:glucose-regulated proteins; C574057:perthamide C; D000077143:Docetaxel; C112765:tanespimycin; D002945:Cisplatin