Inhibitory properties of nucleic acid-binding ligands on protein synthesis.
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.
Malina
Abba
A
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Que., Canada H3G 1Y6.
Khan
Shakila
S
Carlson
Coby B
CB
Svitkin
Yuri
Y
Harvey
Isabelle
I
Sonenberg
Nahum
N
Beal
Peter A
PA
Pelletier
Jerry
J
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
D000166:Acridines; D000998:Antiviral Agents; D007364:Intercalating Agents; D008024:Ligands; D011500:Protein Synthesis Inhibitors; D014764:Viral Proteins; D000167:Acriflavine; D010458:Peptidyl Transferases