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.

Computational approaches in the rational design of improved carbonyl quenchers : focus on histidine containing dipeptides / G. Vistoli, M. Colzani, A. Mazzolari, D.D. Maddis, G. Grazioso, A. Pedretti, M. Carini, G. Aldini. - In: FUTURE MEDICINAL CHEMISTRY. - ISSN 1756-8919. - 8:14(2016 Sep), pp. 1721-1737.

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

G. Vistoli
Primo
;
M. Colzani
Secondo
;
A. Mazzolari;G. Grazioso;A. Pedretti;M. Carini
Penultimo
;
G. Aldini
Ultimo
2016

Abstract

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.
carbonyl quenching; carnosine derivatives; high-resolution mass spectrometry; property space; reactive carbonyl species; reactivity parameters
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/435999
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