Internalization of a peptide into multilamellar vesicles assisted by the formation of an alpha-oxo oxime bond.
As part of a drug-delivery project, we designed and synthesised a novel hydroxylamine cholesterol-based anchor to ensure the chemoselective ligation of recognition patterns onto multilamellar vesicles by oxime ligation. The entry of a glyoxylyl peptide into the vesicles was unexpectedly assisted by the formation of the alpha-oxo oxime bond. We studied extensively the kinetic and thermodynamic aspects of this phenomenon. Briefly, for a glyoxylyl peptide, the speed and ability to enter the vesicle were dependent upon 1) the presence of a hydroxylamine anchor of the type CholE3ONH2, 2) the amount of peptide engaged in the ligation and 3) the flip-flop motion permitted by the different formulations, in which the presence of cholesterol seems to play an important role.
Richard
Antoine
A
UMR 8525 CNRS/Université de Lille 2, Faculté de Pharmacie de Lille, 3, rue du Pr. Laguesse, BP83, 59006 Lille Cedex, France.
Bourel-Bonnet
Line
L
D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010091:Oximes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D016339:Spectrometry, Mass, Fast Atom Bombardment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010091:Oximes; D010455:Peptides