RESUMEN
The interaction of new bivalent NOP receptor antagonists with dodecyl phosphatidylcholine micelles and DMPC/cholesterol liposomes was investigated in solution by high resolution NMR. The ligands are structurally related to the NOP antagonist JTC-801 plus a propanediamine or heptanediamine spacer between the pharmacophoric units. Ligand internuclear distances were derived from 2D NOESY data and applied to molecular modelling calculations as conformational restraints. NMR experiments on micelles evidenced that the ligands closely approached the micelles but gave no hints on the preferential conformations of the interacting ligands. Results from NMR experiments in the presence of liposomes clearly indicated that both ligands strongly interacted with the bilayer assuming a preferential folded conformation with the quinoline arms superimposing on each other. The finding suggested that these strongly lipophilic pharmacophores could localize in the native receptorial membrane in the form of a depot, gaining access to the recognition site via the lipid bilayer.
Asunto(s)
Membrana Dobles de Lípidos/química , Antagonistas de Narcóticos/química , Antagonistas de Narcóticos/farmacología , Quinolinas/química , Quinolinas/farmacología , Colesterol/química , Dimiristoilfosfatidilcolina/química , Humanos , Ligandos , Liposomas/química , Micelas , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular , Fosfatidilcolinas/química , Receptores Opioides/metabolismo , Receptor de NociceptinaRESUMEN
An amidic derivative of a carboxymethylcellulose-based hydrogel was obtained and characterized in terms of amidation degree. NMR studies and FT-IR imaging spectroscopy demonstrated that the reaction allowed a polymer to be obtained that was characterized by a regular distribution of amidic groups along the polysaccharide chains. Through this regularity, a homogenous three-dimensional scaffold was obtained, which maintained the thixotropic property of the linear polysaccharide.