Medicinal Chemistry Research

, Volume 21, Issue 12, pp 4430–4436

Scouting new molecular targets for CFTR therapy: the HSC70/BAG-1 complex. A computational study

  • Elena Cichero
  • Anna Basile
  • Maria Caterina Turco
  • Mauro Mazzei
  • Paola Fossa
Original Research

DOI: 10.1007/s00044-012-9985-1

Cite this article as:
Cichero, E., Basile, A., Turco, M.C. et al. Med Chem Res (2012) 21: 4430. doi:10.1007/s00044-012-9985-1
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Abstract

HSC70 has been identified as an important molecular target involved in the ΔF508-CFTR cystic fibrosis. HSC70 associates ΔF508-CFTR to a much greater extent than WT-CFTR and after this step, it recruits other co-chaperones (BAG1, CHIP) and performs the ubiquitination and proteosomal degradation of the protein. Up to now, several X-ray data concerning the HSC70:BAG1 complexes are available. Thus, we performed an “in silico” investigation focused to explore which different amino acid residues are involved in the binding of ATP, the natural substrate, and the co-crystallized ligands at the HSC70/BAG-1 interface. The study allowed us to evaluate sildenafil and KM11060, which proved to be also CFTR correctors, as potential HSC70:BAG1 inhibitors, and also let us derive interesting perspectives for the development of new CFTR correctors.

Keywords

CFTRHSC70BAG-1Computational study

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Elena Cichero
    • 1
  • Anna Basile
    • 2
    • 3
  • Maria Caterina Turco
    • 2
    • 3
  • Mauro Mazzei
    • 1
  • Paola Fossa
    • 1
  1. 1.Dipartimento di Scienze FarmaceuticheUniversità di GenovaGenoaItaly
  2. 2.Dipartimento di Scienze Farmaceutiche (FARMABIOMED)Università di Salerno—Via Ponte Don MelilloFiscianoItaly
  3. 3.Biouniversa SrlSalernoItaly