RESUMO
The possibility of organizing detergent-solubilized membrane proteins in a plane within the core of Newton black films (NBFs) formed from fluorinated surfactants has been investigated. Fluorinated surfactants have the interesting characteristics of being poorly miscible with detergents and highly surface-active. As a result, when a membrane protein-the transmembrane domain of OmpA (tOmpA)-solubilized by the nonionic detergent C8E4 (tetraethylene glycol monooctyl ether) was injected under a monolayer of fluorinated surfactant, C8E4 and tOmpA/C8E4 complexes remained confined to the subphase. Vertical, macroscopic NBFs were drawn, and their structure was investigated by means of X-ray reflectivity. Depending on experimental conditions, the protein was shown to organize into either one or two monolayers stabilized by two monolayers of fluorinated surfactant. Two different mechanisms of protein insertion were investigated: (i) attachment of polyhistidine-tagged tOmpA/C8E4 complexes to nickel-bearing polar groups born by a fluorinated surfactant and (ii) spontaneous diffusion into the surfactant films. Possible applications are discussed.
Assuntos
Proteínas da Membrana Bacteriana Externa/química , Físico-Química/métodos , Detergentes/química , Flúor/química , Tensoativos/química , Detergentes/farmacologia , Histidina/química , Lipoproteínas/química , Proteínas de Membrana/química , Micelas , Modelos Químicos , Níquel , Dobramento de Proteína , Proteínas/química , Propriedades de Superfície , Raios XRESUMO
The synthesis of a new fluorocarbon amphiphilic drug carrier is described. A polyfunctional amino acid endowed with a fluorocarbon chain and a sugar moiety providing the amphiphilic character constitutes the central element of this structure. A (14)C-radiolabelled acetyl group was grafted onto the third function and the bioavailability of this molecule was specified in mice after IV administration. This amphiphilic drug carrier exhibits a rapid and homogeneous distribution to the whole tissues and slow elimination half-lives (higher than one day) through a biliary excretion without any toxicity (no measured DL 50 for concentrations up to 500 mg/kg).
Assuntos
Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Desenho de Fármacos , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Meia-Vida , Masculino , Camundongos , Estrutura Molecular , Nanoestruturas , Transplante de Neoplasias , Tensoativos/síntese química , Tensoativos/química , Tensoativos/farmacocinéticaRESUMO
Work reported herein deals with the synthesis and preliminary biological assessments of a new class of biocompatible telomeric carriers bearing peptidic RGDSK sequences as tumor cell targeting and tyrosine moieties labelled with 125I as in vivo probe. The radioactivity levels obtained in several tissues, after the intravenous injections of these telomers in mice bearing grafted B16 syngenic melanoma showed that the addition of a RGD residue to a telomeric structure confers it an increased affinity for the highly vascularized zone surrounding the tumor.
