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Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches.
Hyeon, Jae Wook; Choi, Jiwon; Kim, Su Yeon; Govindaraj, Rajiv Gandhi; Jam Hwang, Kyu; Lee, Yeong Seon; An, Seong Soo A; Lee, Myung Koo; Joung, Jong Young; No, Kyoung Tai; Lee, Jeongmin.
Afiliación
  • Hyeon JW; Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control &Prevention, Chungcheongbuk-do 363-700, Korea.
  • Choi J; Bioinformatics &Molecular Design Research Center, Seoul, 120-749, Korea.
  • Kim SY; Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control &Prevention, Chungcheongbuk-do 363-700, Korea.
  • Govindaraj RG; Bioinformatics &Molecular Design Research Center, Seoul, 120-749, Korea.
  • Jam Hwang K; Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control &Prevention, Chungcheongbuk-do 363-700, Korea.
  • Lee YS; Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control &Prevention, Chungcheongbuk-do 363-700, Korea.
  • An SS; GachonBioNano Research Institute, Gachon University, Gyeonggi-do 461-701, Korea.
  • Lee MK; College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
  • Joung JY; Nano/Bio Computational Chemistry Laboratory, Department of Chemistry, Sookmyung Woman's University, Seoul, 140-742, Korea.
  • No KT; Bioinformatics &Molecular Design Research Center, Seoul, 120-749, Korea.
  • Lee J; Department of Biotechnology, Yonsei University, Seoul, 120-749, Korea.
Sci Rep ; 5: 14944, 2015 Oct 09.
Article en En | MEDLINE | ID: mdl-26449325
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación por Computador / Xenobióticos / Proteínas PrPSc / Proteínas PrPC / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación por Computador / Xenobióticos / Proteínas PrPSc / Proteínas PrPC / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido