title: Inhibitory properties of nucleic acid-binding ligands on protein synthesis.
abstract: The use of small molecule inhibitors in the study of cellular processes is a powerful approach to understanding gene function. During the course of a high throughput screen for novel inhibitors of eukaryotic translation, we identified a number of nucleic acid binding ligands that showed activity in our assay. When tested on a panel of mRNA transcripts displaying different modes of translation initiation, these ligands showed a range of biological activities--with some inhibiting both cap-dependent and internal initiation and others preferentially blocking internal initiation. We used this information to identify a novel threading intercalator that inhibits Hepatitis C virus internal initiation.
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Que., Canada H3G 1Y6.
authors.forename: Abba
authors.initials: A
authors.lastname: Malina
authors.forename: Shakila
authors.initials: S
authors.lastname: Khan
authors.forename: Coby B
authors.initials: CB
authors.lastname: Carlson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Svitkin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Harvey
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Peter A
authors.initials: PA
authors.lastname: Beal
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D000166:Acridines / Q000737:chemistry; D000167:Acriflavine / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D008024:Ligands; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D000166:Acridines; D000998:Antiviral Agents; D007364:Intercalating Agents; D008024:Ligands; D011500:Protein Synthesis Inhibitors; D014764:Viral Proteins; D000167:Acriflavine; D010458:Peptidyl Transferases