Computational approaches in the rational design of improved carbonyl quenchers: focus on histidine containing dipeptides.

AIM

The inhibition of protein carbonylation can play therapeutic roles in several oxidative-based diseases and direct carbonyl quenching appears the most effective inhibition strategies. l-carnosine derivatives are effective and selective quenchers toward 4-hydroxy-2-nonenal even though their activity was never investigated in a fully comparable way.

RESULTS

The reported results revealed that anserine, homocarnosine and carnosinamide retain a remarkable quenching activity combined with a satisfactory selectivity. In silico analyses confirmed the key role of flexibility, lipophilicity and nucleophilicity parameters in rationalizing the measured reactivity.

CONCLUSION

This study confirms that in silico approaches can be successfully used in the rational design of improved carbonyl quenchers. Physicochemical and stereoelectronic descriptors appear really informative especially when explored by their corresponding property spaces.