title: Selection of small peptides, inhibitors of translation.
abstract: Identification of small molecular weight compounds targeting specific sites in the ribosome can accelerate development of new antibiotics and provide new tools for ribosomal research. We demonstrate here that antibiotic-size short peptides capable of inhibiting protein synthesis can be selected by using specific elements of ribosomal RNA as a target. The 'h18' pseudoknot encompassing residues 500-545 of the small ribosomal subunit RNA was used as a target in screening a heptapeptide phage-display library. Two of the selected peptides could efficiently interfere with both bacterial and eukaryotic translation. One of these inhibitory peptides exhibited a high-affinity binding to the isolated small ribosomal subunit (K(d) of 1.1 microM). Identification of inhibitory peptides that likely target a specific rRNA structure may pave new ways for validating new antibiotic sites in the ribosome. The selected peptides can be used as a tool in search of novel site-specific inhibitors of translation.
authors: Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, 60607, USA.
authors: Beatriz
authors: B
authors: Llano-Sotelo
authors: Dorota
authors: D
authors: Klepacki
authors: Alexander S
authors: AS
authors: Mankin
mesh_terms: D001483:Base Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D012335:RNA, Ribosomal