Inhibition by suramin of protein synthesis in vitro. Ribosomes as the target of the drug.
Suramin, a drug widely used both as a therapeutic agent and in research, inhibits translation in eukaryotic cell-free systems from rabbit reticulocyte lysate (IC(50)=142-241 microM). Suramin affects both initiation (block of 43S pre-initiation complex formation) and elongation (impairment of poly(U) translation). The drug induces an increase in the pools of ribosomal subunits and the formation of high molecular weight ribosomal complexes, thus causing the disappearance of polysomes. Ribosomes isolated from suramin-treated translating mixtures are inactivated. [(3)H]Suramin binds to ribosomes and to isolated 60S and 40S ribosomal subunits (116, 106 and 3 binding sites, respectively) showing higher affinity for the small subunit (K(d)=2 microM).
Brigotti
Maurizio
M
Dipartimento di Patologia Sperimentale, Università di Bologna, Via San Giacomo 14, 40126 Bologna, Italy. brigotti@alma.unibo.it
Alfieri
Roberta R
RR
Petronini
Pier Giorgio
PG
Carnicelli
Domenica
D
D000818:Animals; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects / Q000502:physiology; D011132:Polyribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013498:Suramin / Q000737:chemistry / Q000494:pharmacology*
D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D013498:Suramin