title: A surface active benzodiazepine receptor ligand for potential probing membrane order of GABAA-receptor surroundings.
abstract: A conjugable analogue of the benzodiazepine 5-(2-hydroxiphenyl)-7-nitro-benzo[ e][1,4]diazepin-2(3 H)-one N 1-substituted with an aliphatic chain (CNZ acyl derivative, CAd) was synthesized. CAd inhibited FNZ binding to GABA A-R with an inhibition binding constant K i = 176 nM and expanded a model membrane packed up to 13 mN/m when penetrating from the aqueous phase. CAd exhibited surface activity with a collapse pressure pi = 18.8 mN/m and minimal molecular area A min = 49 A (2)/molecule at the closest molecular packing, resulting in full and nonideal mixing with a phospholipid in a monolayer up to a molar fraction x congruent with 0.1, decreasing its surface potential and contributing with a dipole that pointed its positive end toward the air and reoriented at the interface upon compression. These findings suggested that CAd could be stabilized at the membrane-water interface with its CNZ moiety stacked at the GABA A-R while its acyl chain can be inserted into the membrane depth.
authors.affiliation: Biofísica-Química, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina.
authors.forename: Anahí V
authors.initials: AV
authors.lastname: Turina
authors.forename: Benjamín
authors.initials: B
authors.lastname: Caruso
authors.forename: Gloria I
authors.initials: GI
authors.lastname: Yranzo
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Moyano
authors.forename: María A
authors.initials: MA
authors.lastname: Perillo
mesh_terms: D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D010743:Phospholipids; D011963:Receptors, GABA-A; D001569:Benzodiazepines