Internalization of a Peptide into Multilamellar Vesicles Assisted by the Formation of an α‐Oxo Oxime Bond

Abstract

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.

α-Oxo Aldehyde or Glyoxylyl Group Chemistry in Peptide Bioconjugation

“…In another application, α-oxo oxime ligation was used to attach a VEGF-R2 binding peptide to the surface of multilamellar vesicles, as a potential way to target the vesicles to angiogenic cells . For this, a hydroxylamine derivative of cholesterol was synthesized and incorporated into the multilamellar vesicles.…”

Planar lamellae and onions: a spatially resolved rheo–NMR approach to the shear-induced structural transformations in a surfactant model system

“…Therefore MLVs, which are metastable and may persist for long times, are investigated as possible containers and delivery systems for drugs and nanoparticles. [5][6][7][8][9][10][11][12][13][14] They also show potential as microreactors.…”

“…Therefore MLVs, which are metastable and may persist for long times, are investigated as possible containers and delivery systems for drugs and nanoparticles. [5][6][7][8][9][10][11][12][13][14] They also show potential as microreactors. 15,16 The initial formation of the onion structure from the ''normal'' L a phase is accompanied by an increase in viscosity.…”

Bioinspired organic chemistry

“…After connection to the sterol, the lipid-peptide conjugates could pass through the membranes of multilamellar vesicles, and since the formation of oxime bonds is reversible, the free glyoxylyl peptides were released within the vesicles. 99 The observation of strong non-covalent interactions between oligo-or poly-arginines and anionic substrates has led to the use of oligo-or poly-arginines as drug delivery agents. The nature of the counterions associated with the guanidinium groups is key, for example the efflux of anionic carboxyfluorescein from vesicles only occurred with counterions, such as a carboxylate-appended fullerene, that were highly amphiphilic.…”