title: Selection of heptapeptides that bind helix 69 of bacterial 23S ribosomal RNA.
abstract: Helix 69 of Escherichia coli 23S rRNA has important roles in specific steps of translation, such as subunit association, translocation, and ribosome recycling. An M13 phage library was used to identify peptide ligands with affinity for helix 69. One selected sequence, NQVANHQ, was shown through a bead assay to interact with helix 69. Electrospray ionization mass spectroscopy revealed an apparent dissociation constant for the amidated peptide and helix 69 in the low micromolar range. This value is comparable to that of aminoglycoside antibiotics binding to the A site of 16S rRNA or helix 69. Helix 69 variants (human) and unrelated RNAs (helix 31 or A site of 16S rRNA) showed two- to fourfold lower affinity for NQVANHQ-NH(2). These results suggest that the peptide has desirable features for development as a lead compound for novel antimicrobials.
authors: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors: Moninderpal
authors: M
authors: Kaur
authors: Chamila N
authors: CN
authors: Rupasinghe
authors: Edvin
authors: E
authors: Klosi
authors: Mark R
authors: MR
authors: Spaller
authors: Christine S
authors: CS
authors: Chow
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D012338:RNA, Ribosomal, 23S
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