PEGylated amyloid peptide nanocontainer delivery and release system.
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.
Castelletto
V
V
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK.
McKendrick
J E
JE
Hamley
I W
IW
Olsson
U
U
Cenker
C
C
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002918:Chymotrypsin / Q000378:metabolism; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004337:Drug Carriers / Q000737:chemistry*; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D053838:Scattering, Small Angle; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D004337:Drug Carriers; D008823:Micelles; D010446:Peptide Fragments; D011092:Polyethylene Glycols; D002918:Chymotrypsin