High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity.

TitleHigh throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity.
Publication TypeJournal Article
Year of Publication2011
AuthorsPatel SM, de la Fuente M, Ke S, Guimarães AMR, Oliyide AO, Ji X, Stapleton P, Osbourn A, Pan Y, Bowles DJ, Davis BG, Schätzlein A, Yang M
JournalChem Commun (Camb)
Volume47
Issue38
Pagination10569-71
Date Published2011 Oct 14
ISSN1364-548X
KeywordsCell Line, Tumor, DNA Topoisomerases, Type II, Drug Screening Assays, Antitumor, Enzyme Inhibitors, Enzymes, Glycosylation, HSP90 Heat-Shock Proteins, Humans, Novobiocin
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.

DOI10.1039/c1cc13552j
Alternate JournalChem. Commun. (Camb.)
PubMed ID21863200
Grant ListBB/D005949/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom