title: Benzene-di-N-octylcarbamates as conformationally constrained phospholipase A(2) inhibitors.
abstract: Conformationally constrained 1,2-, 1,3-, and 1,4-benzene-di-N-octylcarbamates are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A(2) with the K(i) values of 11, 4, and 15 microM, respectively. With the angle of 120(o) between two C(benzene)-O bonds, 1,3-benzene-di-N-octylcarbamate mimics the preferable eclipsed C(sn-2)-O/C(sn-3)-O conformer of phospholipid in the enzyme-phospholipid complex. Further, a three-step phospholipase A(2) inhibition mechanism by the inhibitor is proposed.
authors.affiliation: Department of Chemistry, National Chung-Hsing University, Taichung 402, Taiwan. gilin@dragon.nchu.edu.tw
authors.forename: Gialih
authors.initials: G
authors.lastname: Lin
authors.forename: Yan-Fu
authors.initials: YF
authors.lastname: Lin
authors.forename: Mei-Ting
authors.initials: MT
authors.lastname: Hwang
authors.forename: Yu-Zen
authors.initials: YZ
authors.lastname: Lin
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D002219:Carbamates; D004791:Enzyme Inhibitors; D010743:Phospholipids; D010767:Phosphorylcholine; D010741:Phospholipases A