title: Computational approaches in the rational design of improved carbonyl quenchers: focus on histidine containing dipeptides.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Giulio
authors: G
authors: Vistoli
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Mara
authors: M
authors: Colzani
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Angelica
authors: A
authors: Mazzolari
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Danilo De
authors: DD
authors: Maddis
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Giovanni
authors: G
authors: Grazioso
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Alessandro
authors: A
authors: Pedretti
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Marina
authors: M
authors: Carini
authors: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Giancarlo
authors: G
authors: Aldini
mesh_terms: D000818:Animals; D000861:Anserine / Q000737:chemistry*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry; D003198:Computer Simulation; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D013237:Stereoisomerism
chemical_list: D004151:Dipeptides; C005038:homocarnosine; D006639:Histidine; D002336:Carnosine; D000861:Anserine
keywords: carbonyl quenching; carnosine derivatives; high-resolution mass spectrometry; property space; reactive carbonyl species; reactivity parameters