Novel paromamine derivatives exploring shallow-groove recognition of ribosomal-decoding-site RNA.
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.
Simonsen
Klaus B
KB
Department of Medicinal Chemistry, Anadys Pharmaceuticals, Inc, 9050 Camino Santa Fe, San Diego, CA 92121, USA. ksimonsen@anadyspharma.com
Ayida
Benjamin K
BK
Vourloumis
Dionisios
D
Takahashi
Masayuki
M
Winters
Geoffrey C
GC
Barluenga
Sofia
S
Qamar
Seema
S
Shandrick
Sarah
S
Zhao
Qiang
Q
Hermann
Thomas
T
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; C005936:paromamine