title: Structure-based design of agents targeting the bacterial ribosome.
abstract: Rational structure-based drug design has been applied to the antibiotic thiostrepton, in an attempt to overcome some of its' limitations. The identification of a proposed binding fragment allowed construction of a number of key fragments, which were derivatised to generate a library of potential antibiotics. These were then evaluated to determine their ability to bind to the L11 binding domain of the prokaryotic ribosome and inhibit bacterial protein translation.
authors.affiliation: Department of Medicinal Chemistry, RiboTargets Ltd., Granta Park, Abington, Cambridge CB1 6GB, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Bower
authors.forename: Martin
authors.initials: M
authors.lastname: Drysdale
authors.forename: Richard
authors.initials: R
authors.lastname: Hebdon
authors.forename: Allan
authors.initials: A
authors.lastname: Jordan
authors.forename: Georg
authors.initials: G
authors.lastname: Lentzen
authors.forename: Natalia
authors.initials: N
authors.lastname: Matassova
authors.forename: Alastair
authors.initials: A
authors.lastname: Murchie
authors.forename: Jenifer
authors.initials: J
authors.lastname: Powles
authors.forename: Stephen
authors.initials: S
authors.lastname: Roughley
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000648:ultrastructure; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D007202:Indicators and Reagents; D008745:Methylation; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis / Q000187:drug effects; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013883:Thiostrepton / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D012335:RNA, Ribosomal; D013883:Thiostrepton