title: Identification of novel ligands for the RNA pseudoknot that regulate -1 ribosomal frameshifting.
abstract: In many viruses, -1 ribosomal frameshifting (-1RF) regulates synthesis of proteins and is crucial for virus production. An RNA pseudoknot is one of the essential components of the viral -1RF system. Thermodynamic or kinetic control of pseudoknot folding may be important in regulating the efficiency of -1RF. Thus, small molecules that interact with viral RNA pseudoknots may disrupt the -1RF system and show antiviral activity. In this study, we conducted virtual screening of a chemical database targeting the X-ray crystal structure of RNA pseudoknot complexed with biotin to identify ligands that may regulate an -1RF system containing biotin-aptamer as an RNA pseudoknot component. After docking screening of about 80,000 compounds, 58 high-ranked hits were selected and their activities were examined by in vitro and cell-based -1 frameshifting assays. Six compounds increased the efficiency of -1 frameshifting, and these are novel small molecule compounds that regulate the -1RF.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
authors.forename: Yang-Gyun
authors.initials: YG
authors.lastname: Kim
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D001710:Biotin / Q000737:chemistry; D016208:Databases, Factual; D018965:Frameshifting, Ribosomal; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D008024:Ligands; D012313:RNA; D001710:Biotin