Structure-based design of agents targeting the bacterial ribosome.
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.
Bower
Justin
J
Department of Medicinal Chemistry, RiboTargets Ltd., Granta Park, Abington, Cambridge CB1 6GB, UK.
Drysdale
Martin
M
Hebdon
Richard
R
Jordan
Allan
A
Lentzen
Georg
G
Matassova
Natalia
N
Murchie
Alastair
A
Powles
Jenifer
J
Roughley
Stephen
S
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
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D012335:RNA, Ribosomal; D013883:Thiostrepton