Rotaxane-Based Propeptides: Protection and Enzymatic Release of a Bioactive Pentapeptide


  • We thank Prof. Jean-Pierre Gesson (Poitiers) for many useful discussions and the EPSRC National Mass Spectrometry Service Centre (Swansea, UK) for accurate mass data. This work was supported by the Science and Technology Department of the French Embassy in the United Kingdom, the Scottish Executive and the Royal Society of Edinburgh. D.A.L. is an EPSRC Senior Research Fellow and holds a Royal Society-Wolfson Research Merit Award.


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Ring of protection: A [2]rotaxane 1 protects and selectively releases a bioactive pentapeptide. The rotaxane macrocycle provides a defensive shield that very significantly improves the poor stability of the peptide to both individual peptidases and the cocktail of enzymes present in human plasma. Glycosidase-catalyzed cleavage of a carbohydrate ‘stopper’ in the rotaxane triggers release of the parent peptide (see picture).