title: Synthesis and characterization of an N-acylsulfonamide inhibitor of human asparagine synthetase.
abstract: [structure: see text] The synthesis of N-acylsulfonamide 6, which is an analogue of beta-aspartyl-AMP, is described. This compound appears to be the first and only potent inhibitor of human asparagine synthetase that has been described to date. The N-acylsulfonamide 6 exhibits slow-onset inhibition kinetics, with a K(i) of 728 nM. Preparation and characterization of two additional N-acylsulfonamide analogues has also demonstrated the importance of hydrogen-bonding interactions in the recognition of the AS inhibitor with the enzyme. These observations provide the basis for the discovery of new compounds with application in the treatment of drug-resistant leukemia.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Koroniak
authors.forename: Mihai
authors.initials: M
authors.lastname: Ciustea
authors.forename: Jemy A
authors.initials: JA
authors.lastname: Gutierrez
authors.forename: Nigel G J
authors.initials: NG
authors.lastname: Richards
mesh_terms: D001217:Aspartate-Ammonia Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D013449:Sulfonamides; D001217:Aspartate-Ammonia Ligase