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- Title
Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches.
- Authors
Jae Wook Hyeon; Jiwon Choi; Su Yeon Kim; Govindaraj, Rajiv Gandhi; Kyu Jam Hwang; Yeong Seon Lee; Seong Soo A. An; Myung Koo Lee; Jong Young Joung; Kyoung Tai No; Jeongmin Lee
- Abstract
Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc 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 PrPC interaction with a known antiprion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds.
- Subjects
PRIONS; SURFACE plasmon resonance; SURAMIN; PROTEIN-tyrosine kinases; AMPHOTERICIN B; CLUSTER analysis (Statistics)
- Publication
Scientific Reports, 2015, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep14944