title: High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity.
abstract: Glycosylated analogues of novobiocin, discovered using a broad library of enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung and ovarian cancers and ablated associated off-target activity leading to an up to 2.7 × 10(4) fold increase in selectivity.
authors.affiliation: Department of Pharmaceutical & Biological Chemistry, The School of Pharmacy, University of London, 29/39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: Sital M
authors.initials: SM
authors.lastname: Patel
authors.forename: Maria
authors.initials: M
authors.lastname: de la Fuente
authors.forename: Song
authors.initials: S
authors.lastname: Ke
authors.forename: Andreia M R
authors.initials: AM
authors.lastname: Guimarães
authors.forename: Adeola O
authors.initials: AO
authors.lastname: Oliyide
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ji
authors.forename: Paul
authors.initials: P
authors.lastname: Stapleton
authors.forename: Anne
authors.initials: A
authors.lastname: Osbourn
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Dianna J
authors.initials: DJ
authors.lastname: Bowles
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
authors.forename: Andreas
authors.initials: A
authors.lastname: Schatzlein
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009675:Novobiocin / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D018841:HSP90 Heat-Shock Proteins; D009675:Novobiocin; D004250:DNA Topoisomerases, Type II