Synthesis of new carnosine derivatives of beta-cyclodextrin and their hydroxyl radical scavanger ability

Several in vitro and in vivo studies have suggested that carnosine can act as a scavenger of reactive oxygen species and intracellular proton buffer. On the other hand, carnosinase is a specific peptidase able to destroy the biological active dipeptide. To overcome this constraint, beta-cyclodextrin (beta-CD) was functionalized with carnosine to give the following new compounds: 6(A)-[(3-[[(IS)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino)-3-oxopropyl)amino]-6(A)-1-deoxy-beta-cyclodextrin (1), 6(A)-[ (beta-alanyl-L-histidyl)amino]-beta-cyclodextrin (2), and (2(A)S,3(A)R)-3(A)-[(3-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-3-oxopropyl)amino]-3(A)-deoxy-beta-cyclodextrin (3). Pulse-radiolysis investigation showed that the beta-CD derivatives 1-3 are excellent scavengers of OH, radicals. Their activity is not only due to the formation of the stable imidazole-centered radical, but also to the scavenger ability of the glucose moieties of the macrocycle (Scheme). This effect is independent of the disposition of the imidazole ring. In fact, the quenching constant values are similar for the three compounds.