RESUMEN
A micellar nanocontainer delivery and release system is designed on the basis of a peptide-polymer conjugate. The hybrid molecules self-assemble into micelles comprising a modified amyloid peptide core surrounded by a PEG corona. The modified amyloid peptide previously studied in our group forms helical ribbons based on a beta-sheet motif and contains beta-amino acids that are excluded from the beta-sheet structure, thus being potentially useful as fibrillization inhibitors. In the model peptide-PEG hybrid system studied, enzymatic degradation using alpha-chymotrypsin leads to selective cleavage close to the PEG-peptide linkage, break up of the micelles, and release of peptides in unassociated form. The release of monomeric peptide is useful because aggregation of the released peptide into beta-sheet amyloid fibrils is not observed. This concept has considerable potential in the targeted delivery of peptides for therapeutic applications.
Asunto(s)
Péptidos beta-Amiloides/química , Portadores de Fármacos/química , Nanoestructuras/química , Fragmentos de Péptidos/química , Polietilenglicoles/química , Secuencia de Aminoácidos , Quimotripsina/metabolismo , Dicroismo Circular , Cristalografía por Rayos X , Micelas , Fragmentos de Péptidos/metabolismo , Dispersión del Ángulo Pequeño , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
We study the effects of NaCl on the self-assembly of AAKLVFF and betaAbetaAKLVFF in solution. Both AAKLVFF and betaAbetaAKLVFF self-assemble into twisted fibers in aqueous solution. The addition of NaCl to aqueous solutions of AAKLVFF produces large crystal-like nanotapes which eventually precipitate. In contrast, highly twisted fibrils were observed for betaAbetaAKLVFF solutions at low salt concentration, while a coexistence of highly twisted fibers and nanotubes was observed for betaAbetaAKLVFF at high salt concentration. The self-assembled structures observed for betaAbetaAKLVFF in NaCl solutions were ascribed to the progressive screening of the betaAbetaAKLVFF surface charge caused by the addition of salt.
Asunto(s)
Péptidos beta-Amiloides/química , Secuencia de Aminoácidos , Dicroismo Circular , Nanotubos/química , Nanotubos/ultraestructura , Péptidos/química , Estructura Secundaria de Proteína , Cloruro de Sodio/química , Espectroscopía Infrarroja por Transformada de Fourier , Agua/químicaRESUMEN
The self-assembly of the trifluoroacetate salt of the short peptide (ala)6-lys (A6K) in water has been investigated by cryo-transmission electron microscopy and small-angle X-ray scattering. For concentrations below ca. 12%, the peptide does not self-assemble but forms a molecularly dispersed solution. Above this critical concentration, however, A6K self-assembles into several-micrometer-long hollow nanotubes with a monodisperse cross-sectional radius of 26 nm. Because the peptides carry a positive charge, the nanotubes are charge-stabilized. Because of the very large aspect ratio, the tubes form an ordered phase that presumably is nematic.