Synthesis and antioxidant activity of new homocarnosine beta-cyclodextrin conjugates

Several in vitro and in vivo studies have suggested that carnosine (b-alanil-L-histidine) and homocarnosine (b-aminobutyril-L-histidine) can act as scavengers of reactive oxygen species. b-Cyclodextrin was functionalized with homocarnosine, obtaining the following new bioconjugate isomers: 6A-[(4-{[(1S )-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-6A-deoxy-b-cyclodextrin and (2AS,3AR)- 3A-[(4-{[(1S )-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-3A-deoxy-b-cyclodextrin. Pulse radiolysis investigations show that the b-cyclodextrin homocarnosine bioconjugates are scavengers of OH radicals because of the formation of stable imidazole-centered radicals and the scavenger ability of glucose molecules of the macrocycle. The ability of these new b-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the b-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the b-CD cavity. The ability of these new b-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the b-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the b-CD cavity.