In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2015-10-09)
Abstract:
Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrP C ) to the pathogenic form, PrP Sc . Compounds that inhibit this process by blocking conversion to the PrP Sc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico . Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrP C interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays and surface plasmon resonance. Some compounds effectively reduced PrP Sc levels and one of these compounds also showed a high binding affinity for PrP C . These results provide a promising starting point for the development of anti-prion compounds.
Type of Medium:
Online Resource
ISSN:
2045-2322
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2015
detail.hit.zdb_id:
2615211-3
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