Design and biological activity of imidazole-containing peptidomimetics with a broad-spectrum antioxidant activity

Abstract

Histidine-containing natural dipeptides, such as L-carnosine, were reported to be effective against different oxygenderived free radicals, and also lipoperoxyl radicals. However, L-carnosine appeared to be uneffective in vivo, due to the presence of ubiquitous specific or semi-specific hydrolytic enzymes. Therefore, a series of peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis. Some structural modifications were also done in an attempt to improve the antioxidant power of the molecule, for example, in relation to binding of ferrous ions. The following methods were used for the evaluation of peptidomimetics: 0 It was shown that decarboxylation of L-carnosine results in an important improvement of the resistance towards hydrolytic enzymes. In vitro experiment have demonstrated, for a series of peptidomimetrics free radical scavenging and lipid hydroperoxide deactivating properties similar to or even better than the natural peptide (depending on the experimental design). In addition, the two peptidomimetics β-alanylhistamine and L-prolylhistamine proved to be far superior in inhibiting the lipid hydroperoxide-mediated cross-linking of a representative protein. Finally, β-alanylhistamine was able to protect skin enzymes from UV-induced degradations in vivo.