Your browser doesn't support javascript.
loading
A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.
Kirby, Karen A; Myshakina, Nataliya A; Christen, Martin T; Chen, Yue-Lei; Schmidt, Hilary A; Huber, Andrew D; Xi, Zhaoyong; Kim, Seongmi; Rao, Rohit K; Kramer, Skyler T; Yang, Qiongying; Singh, Kamalendra; Parniak, Michael A; Wang, Zhengqiang; Ishima, Rieko; Sarafianos, Stefan G.
Afiliação
  • Kirby KA; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA kirbyk@missouri.edu sarafianoss@missouri.edu.
  • Myshakina NA; Department of Molecular Microbiology & Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
  • Christen MT; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Chen YL; Department of Natural Science, Chatham University, Pittsburgh, Pennsylvania, USA.
  • Schmidt HA; Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Huber AD; Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Xi Z; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
  • Kim S; Department of Biological Engineering, University of Missouri, Columbia, Missouri, USA.
  • Rao RK; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
  • Kramer ST; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
  • Yang Q; Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Singh K; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
  • Parniak MA; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
  • Wang Z; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
  • Ishima R; Department of Molecular Microbiology & Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
  • Sarafianos SG; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
Antimicrob Agents Chemother ; 61(10)2017 10.
Article em En | MEDLINE | ID: mdl-28760905
ABSTRACT
The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential part in the viral life cycle. We report the characterization of YLC2-155, a 2-hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155 inhibits both polymerase (50% inhibitory concentration [IC50] = 2.6 µM) and RNH functions (IC50 = 0.65 µM) of RT but is more effective against RNH. X-ray crystallography, nuclear magnetic resonance (NMR) analysis, and molecular modeling were used to show that YLC2-155 binds at the RNH-active site in multiple conformations.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 / Ribonuclease H / Inibidores da Transcriptase Reversa / Fármacos Anti-HIV / Domínio Catalítico / Transcriptase Reversa do HIV / Isoquinolinas Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 / Ribonuclease H / Inibidores da Transcriptase Reversa / Fármacos Anti-HIV / Domínio Catalítico / Transcriptase Reversa do HIV / Isoquinolinas Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article