New glycosidic derivatives of histidine-containing dipeptides with antioxidant properties and resistant to carnosinase activity

Synthesis, antioxidant properties and resistance to carnosinase hydrolysis of histidine-containing dipeptides are reported in this study. Carnosine (β-alanyl-l-histidine), homocarnosine (γ-aminobutyryl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) were covalently derivatized with β-cyclodextrin to form different OH- or NH-bound conjugates. Mass spectroscopic and 1H NMR data were used to determine the structure and the purity of the various β-cyclodextrin derivatives. The inhibitory effect towards oxidation of human LDL induced by Cu2+ ions, was estimated by measuring malondialdehyde formation as a function of increasing concentrations of these newly synthesized compounds (the β-cyclodextrin-anserine conjugated in 3 had the highest antioxidant effect). All derivatives had higher antioxidant effects than those of the corresponding free histidine-containing dipeptides. Resistance to rat brain carnosinase hydrolysis of the most active derivatives indicated that these compounds are good candidates for further studies in more complex cellular and animal models. Their possible applications for remedies in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are discussed.

Graphical abstractThe new anserine cyclodextrin derivatives show antioxidant activity towards copper-induced human LDL oxidation. These compounds are also resistant to the hydrolysis induced by rat brain homogenates.Figure optionsDownload full-size imageDownload as PowerPoint slide