title: Benzene-di-N-substituted carbamates as conformationally constrained substrate analogs of cholesterol esterase.
abstract: Benzene-1,2-, 1,3-, and 1,4-di-N-substituted carbamates (1-15) are synthesized as the constrained analogs of gauche, eclipsed, and anti conformations, respectively, for the glycerol backbones of triacylglycerol. Carbamates 1-15 are characterized as the pseudo substrate inhibitors of cholesterol esterase. Long chain carbamates are more potent inhibitors than short chain ones. Comparison of different geometries for benzene-di-substituted carbamates, such as benzene-1,2-di-N-octylcarbamate (3) (ortho-3), benzene-1,3-di-N-octylcarbamate (8) (meta-8), and benzene-1,4-di-N-octylcarbamates (13) (para-13), indicates that inhibitory potencies are as followed: meta-8 > para-13 > ortho-3. Therefore, we suggest that the preferable conformation for the C(sn-1)-O/C(sn-2)-O glycerol backbone in the enzyme-triacylgycerol complex is the eclipsed conformation. Meanwhile, kinetic data indicate that among ortho, meta, and para carbamates, meta carbamates most resemble the substrate cholesterol ester.
authors.affiliation: Division of Neurosurgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Chiou
authors.forename: M-C
authors.initials: MC
authors.lastname: Lin
authors.forename: M-T
authors.initials: MT
authors.lastname: Hwang
authors.forename: H-G
authors.initials: HG
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Lin
mesh_terms: D001554:Benzene / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism*; D008968:Molecular Conformation; D002787:Sterol Esterase / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D002219:Carbamates; D002787:Sterol Esterase; D001554:Benzene