title: Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance.
abstract: Three sets of novel 4-deoxy-l-arabinose analogs were synthesized and evaluated as potential inhibitors of the bacterial resistance mechanism in which lipid A, on the outer membrane, is modified with 4-amino-4-deoxy-l-arabinose (l-Ara4N). One compound diminished the transfer of l-Ara4N onto lipid A. These results suggest that small molecules might be designed that would effect the same reversal of bacterial resistance observed in genetic knockouts.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kline
authors.forename: M S
authors.initials: MS
authors.lastname: Trent
authors.forename: C M
authors.initials: CM
authors.lastname: Stead
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: M C
authors.initials: MC
authors.lastname: Sousa
authors.forename: H B
authors.initials: HB
authors.lastname: Felise
authors.forename: H V
authors.initials: HV
authors.lastname: Nguyen
authors.forename: S I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001089:Arabinose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001386:Azides / Q000138:chemical synthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors; D008050:Lipid A / Q000378:metabolism*; D011113:Polymyxins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001386:Azides; D008050:Lipid A; D011113:Polymyxins; D001089:Arabinose; D006602:Hexosyltransferases; C442226:L-Ara4N transferase