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

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journal contribution
posted on 17.09.2008, 00:00 authored by Anahí V. Turina, Benjamín Caruso, Gloria I. Yranzo, Elizabeth L. Moyano, María A. Perillo
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.