2. Academic Validation
  3. Molecular insights to the bioactive form of BV02, a reference inhibitor of 14-3-3σ protein-protein interactions

Molecular insights to the bioactive form of BV02, a reference inhibitor of 14-3-3σ protein-protein interactions

  • Bioorg Med Chem Lett. 2016 Feb 1;26(3):894-898. doi: 10.1016/j.bmcl.2015.12.066.
Daniela Valensin 1,  Ylenia Cau 1,  Pierpaolo Calandro 1,  Giulia Vignaroli 1,  Lucia Dello Iacono 1,  Mario Chiariello 2,  Mattia Mori 3,  Maurizio Botta 4
Affiliations

Affiliations

  • 1 Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli studi di Siena, via A. Moro snc, Via Aldo Moro 2, 53100 Siena, Italy.
  • 2 Istituto Toscano Tumori, Core Research Laboratory and Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica, sede di Siena, Via Fiorentina 1, 53100 Siena, Italy.
  • 3 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.
  • 4 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: [email protected].
PMID: 26774582 DOI: 10.1016/j.bmcl.2015.12.066
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.

Keywords

14-3-3; Bioactive form; Chemical instability; Chemical transformation; Drug discovery; Lead compound; NMR.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101985
    99.85%, 14-3-3 PPI Inhibitor