title: Molecular insights to the bioactive form of BV02, a reference inhibitor of 14-3-3σ protein-protein interactions.
abstract: BV02 is a reference inhibitor of 14-3-3 protein-protein interactions, which is currently used as chemical biology tool to understand the role of 14-3-3 proteins in pathological contexts. Due to chemical instability in certain conditions, its bioactive form has remained unclear. Here, we use NMR spectroscopy to prove for the first time the direct interaction between the molecule and 14-3-3σ, and to depict its bioactive form, namely the phthalimide derivative 9. Our work provides molecular insights to the bioactive form of the 14-3-3 PPI inhibitor and facilitates further development as candidate therapeutic agent.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Cau
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Calandro
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vignaroli
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Dello Iacono
authors.affiliation: Istituto Toscano Tumori, Core Research Laboratory and Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica, sede di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiariello
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Roma, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Mori
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA. Electronic address: botta.maurizio@gmail.com.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D010797:Phthalimides / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; C557642:BV02 compound; D001549:Benzamides; D010797:Phthalimides; D011720:Pyrazoles; C037431:phthalimide
keywords: 14-3-3; Bioactive form; Chemical instability; Chemical transformation; Drug discovery; Lead compound; NMR