A Surface Active Benzodiazepine Receptor Ligand for Potential Probing Membrane Order of GABAA-Receptor Surroundings

TURINA A.V.; CARUSO B.; YRANZO G.I.; MOYANO E.L.; PERILLO M.A.

Bioconjugate Chemistry

ACS publications

Lugar: California; Año: 2008

1043-1802

A conjugable analogue of the benzodiazepine 5-(2-hydroxiphenyl)-7-nitro-benzo[e][1,4]diazepin-2(3H)-one N1-substituted with an aliphatic chain (CNZ acyl derivative, CAd) was synthesized. CAd inhibited FNZ binding to GABAA-R with an inhibition binding constant Ki ) 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 π ) 18.8 mN/m and minimal molecular area Amin ) 49 Å2/molecule at the closest molecular packing, resulting in full and nonideal mixing with a phospholipid in a monolayer up to a molar fraction x = 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 GABAA-R while its acyl chain can be inserted into the membrane depth.e][1,4]diazepin-2(3H)-one N1-substituted with an aliphatic chain (CNZ acyl derivative, CAd) was synthesized. CAd inhibited FNZ binding to GABAA-R with an inhibition binding constant Ki ) 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 π ) 18.8 mN/m and minimal molecular area Amin ) 49 Å2/molecule at the closest molecular packing, resulting in full and nonideal mixing with a phospholipid in a monolayer up to a molar fraction x = 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 GABAA-R while its acyl chain can be inserted into the membrane depth.