Enhanced Accessibility of Peptide Substrate toward Membrane-Bound Metalloexopeptidase by Supramolecular Structure of Polyrotaxane

• Published in: Biomacromolecules Vol. 2; no. 1; pp. 200 - 203
• Main Authors: Ooya, Tooru, Eguchi, Masaru, Yui, Nobuhiko
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 2001
• Subjects: Cell Membrane - enzymology; Chromatography, Gel; Cyclodextrins - chemistry; Exopeptidases - metabolism; Magnetic Resonance Spectroscopy; Molecular Structure; Oligopeptides - chemistry; Peptides - metabolism; Polyethylene Glycols - chemistry
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm005618f

A l-phenylalanlylglycylglycine- (H−l-PheGlyGly-) terminated polyrotaxane in which many α-cyclodextrins (α-CDs) are threaded onto poly(ethylene oxide) (PEO) was synthesized to evaluate the effect of α-CD threading on the degradation of the terminal H−l-PheGlyGly by a membrane-bound metalloexopeptidase (aminopeptidase M). The threading of α-CDs and introducing H−l-PheGlyGly to the terminals were confirmed by gel permeation chromatography and 1H 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:  ∼16 000). This finding provides a new design of biodegradable polymers for biomedical applications with controlled degradation profile.