title: Novel paromamine derivatives exploring shallow-groove recognition of ribosomal-decoding-site RNA.
abstract: Natural aminoglycoside antibiotics recognize an internal loop of bacterial ribosomal-decoding-site RNA by binding to the deep groove of the RNA structure. We have designed, synthesized, and tested RNA-targeted paromamine derivatives that exploit additional interactions on the shallow groove face of the decoding-site RNA. An in vitro transcription-translation assay of a series of 6'-derivatives showed the 6'-position to be very sensitive to substitution. This result suggests that the group at the 6'-position plays a pivotal role in RNA target recognition.
authors.affiliation: Department of Medicinal Chemistry, Anadys Pharmaceuticals, Inc, 9050 Camino Santa Fe, San Diego, CA 92121, USA. ksimonsen@anadyspharma.com
authors.forename: Klaus B
authors.initials: KB
authors.lastname: Simonsen
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Ayida
authors.forename: Dionisios
authors.initials: D
authors.lastname: Vourloumis
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Winters
authors.forename: Sofia
authors.initials: S
authors.lastname: Barluenga
authors.forename: Seema
authors.initials: S
authors.lastname: Qamar
authors.forename: Sarah
authors.initials: S
authors.lastname: Shandrick
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry; D001665:Binding Sites; D002474:Cell-Free System; D015195:Drug Design; D014176:Protein Biosynthesis / Q000187:drug effects; D012329:RNA, Bacterial / Q000037:antagonists & inhibitors; D012335:RNA, Ribosomal / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000648:ultrastructure; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; C005936:paromamine