Second generation specific-enzyme-activated rotaxane propeptides

A [2] rotaxane, in which the peptidic axle is protected from degradation by the macrocyclic sheath and terminated with a novel glycosidase-cleavable stopper, is rendered water-soluble by derivatisation with tetra(ethylene glycol) (TetEG) or glucosylated tetra(ethylene glycol) (Glc-TetEG) chains using the CuAAC 'click' reaction. The Glc-TetEG-derivatised rotaxane propeptide is > 50 000 times more soluble in aqueous media than the parent rotaxane. Activation of the water-soluble rotaxane propeptide with a beta-galactosidase efficiently releases the parent peptide.