title: Synthesis and structure-activity relationships of truncated bisubstrate inhibitors of aminoglycoside 6'-N-acetyltransferases.
abstract: Truncated aminoglycoside-coenzyme A bisubstrate analogues were efficiently prepared using a convergent approach where the amine and the thiol are coupled in one pot with the addition of a linker, without the need for protecting groups. These derivatives were tested for their effect on the activity of the resistance-causing enzyme aminoglycoside 6'-N-acetyltransferase Ii, and key structure-activity relationships are reported. Moreover, one of the inhibitors is able to block aminoglycoside resistance in cells expressing this enzyme.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Québec H3A 2K6, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xuxu
authors.initials: X
authors.lastname: Yan
authors.forename: Tushar
authors.initials: T
authors.lastname: Shakya
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Baettig
authors.forename: Samia
authors.initials: S
authors.lastname: Ait-Mohand-Brunet
authors.forename: Albert M
authors.initials: AM
authors.lastname: Berghuis
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
authors.forename: Karine
authors.initials: K
authors.lastname: Auclair
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003065:Coenzyme A / Q000737:chemistry*; D016984:Enterococcus faecium / Q000187:drug effects / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D004791:Enzyme Inhibitors; D007612:Kanamycin; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase; D003065:Coenzyme A