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 H-1 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: similar to 16 000). This finding provides a new design of biodegradable polymers for biomedical applications with controlled degradation profile.