Enhanced accessibility of peptide substrate toward membrane-bound metalloexopeptidase by supramolecular structure of polyrotaxane.
A L-phenylalanlylglycylglycine- (H-L-PheGlyGly-) terminated polyrotaxane in which many alpha-cyclodextrins (alpha-CDs) are threaded onto poly(ethylene oxide) (PEO) was synthesized to evaluate the effect of alpha-CD threading on the degradation of the terminal H-L-PheGlyGly by a membrane-bound metalloexopeptidase (aminopeptidase M). The threading of alpha-CDs and introducing H-L-PheGlyGly to the terminals were confirmed by gel permeation chromatography and (1)H NMR spectroscopies. In vitro degradation and kinetic studies revealed that the supramolecular structure of the polyrotaxane enhanced the accessibility toward aminopeptidase M despite the higher molecular weight of the polyrotaxane (M(n): approximately 16,000). This finding provides a new design of biodegradable polymers for biomedical applications with controlled degradation profile.
Ooya
T
T
School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan.
Eguchi
M
M
Yui
N
N
D002462:Cell Membrane / Q000201:enzymology*; D002850:Chromatography, Gel; D003505:Cyclodextrins / Q000737:chemistry*; D020689:Exopeptidases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*
D003505:Cyclodextrins; D009842:Oligopeptides; D010455:Peptides; D011092:Polyethylene Glycols; D020689:Exopeptidases