title: Synthesis and structure-activity relationships of o-sulfonamido-arylhydrazides as inhibitors of LL-diaminopimelate aminotransferase (LL-DAP-AT).
abstract: Recently, LL-diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal-5'-phosphate (PLP)-dependent enzyme, was reported to catalyze a key step in the biosynthesis of L-lysine in plants and Chlamydia. Previous screening of a 29,201-compound library against LL-DAP-AT identified an o-sulfonamidoarylhydrazide as a reversible inhibitor with IC(50)∼ 5 μM. Structure-activity relationship (SAR) studies based on this lead compound identified key structural features essential for enzyme inhibition and led to slightly improved inhibitors. Preliminary studies on the mode of inhibition of LL-DAP-AT by this class of compounds are also reported.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Fan
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D000586:Amination; D017360:Arabidopsis / Q000201:enzymology; D001547:Benzaldehydes / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D000637:Transaminases / Q000037:antagonists & inhibitors*
chemical_list: D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D006834:Hydrazines; C029424:hydrazine; C000062:2-aminobenzaldehyde; D000637:Transaminases