Rational ligand design for RNA: the role of static structure and conformational flexibility in target recognition.
The role of static structure and conformational flexibility in the recognition of RNA targets by small molecule ligands is discussed with emphasis on the natural aminoglycoside antibiotics and their promiscuity in RNA target binding. A brief overview is given of previous efforts to design simplified aminoglycoside derivatives targeted at the bacterial decoding site RNA.
Hermann
Thomas
T
Department of Computational Chemistry and Structure, Anadys Pharmaceuticals, Inc., 9050 Camino Santa Fe, San Diego, CA 92121, USA. thermann@anadyspharma.com
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008024:Ligands; D012335:RNA, Ribosomal; D014867:Water; D012313:RNA