A surface active benzodiazepine receptor ligand for potential probing membrane order of GABAA-receptor surroundings.
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.
Turina
Anahí V
AV
Biofísica-Química, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina.
Caruso
Benjamín
B
Yranzo
Gloria I
GI
Moyano
Elizabeth L
EL
Perillo
María A
MA
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
D008024:Ligands; D008051:Lipid Bilayers; D010743:Phospholipids; D011963:Receptors, GABA-A; D001569:Benzodiazepines