1. Highly cytotoxic and neurotoxic acetogenins of the Annonaceae: New putative biological targets of squamocin detected by activity-based protein profiling
- Author
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Santos A. Susin, Séverine Derbré, Myriam Taverna, Céline Boursier, Reynald Hocquemiller, Joëlle Vinh, Erwan Poupon, Sophie Gil, Valérie Nicolas, Emmanuelle Demey-Thomas, Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Barrières et passage des médicaments, Université Paris-Sud - Paris 11 (UP11), Protéines et Nanotechnologies en Sciences Séparatives, Neurobiologie et diversité cellulaire (NDC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Apoptose et Système Immunitaire (ASI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Acetogenins ,Clinical Biochemistry ,Annonaceae ,Pharmaceutical Science ,010402 general chemistry ,Proteomics ,01 natural sciences ,Biochemistry ,Lactones ,chemistry.chemical_compound ,Polyketide ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Drug Discovery ,medicine ,Furans ,Molecular Biology ,Neurons ,Microscopy, Confocal ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Activity-based proteomics ,Proteins ,Biological activity ,biology.organism_classification ,Mitochondria ,0104 chemical sciences ,3. Good health ,Kinetics ,Mechanism of action ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Acetogenin ,Proteome ,Molecular Medicine ,Electrophoresis, Polyacrylamide Gel ,medicine.symptom - Abstract
International audience; Acetogenins of the Annonaceae are strong inhibitors of mitochondrial complex I but discrepancies in the structure/activity relationships pled the search for other targets within the whole cell proteome. Combining hemisynthetic work, Cu-catalyzed Huisgen cycloaddition and proteomic techniques we have identified new putative protein targets of squamocin ruling out the previously accepted 'complex I dogma'. These results give new insights into the mechanism of action of these potent neurotoxic molecules.
- Published
- 2008
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