Carnosine (β-alanyl-L-histidine) and related peptides such as homocarnosine (γ-amino-butyryl-histidine), balenine β-alanyl-L-3-methylhistidine) and anserine β-alanyl-L-1-methylhistidine) are histidine-containing dipeptides (HD) particularly abundant in excitable tissues such as nervous system and skeletal muscle. Although their biochemical role is still unknown, several evidences indicate that these endogenous compounds act as quenchers of reactive and cytotoxic carbonyl species. In this presentation we will review the structural evidences and ex vivo data supporting this hypothesis. We first elucidated the reaction mechanism of carnosine as quencher of α, β-unsaturated aldehydes such as 4-hydroxy-trans-2,3-nonenal (HNE) and acrolein (ACR) and then demonstrated the efficacy of carnosine and related peptides as detoxifying agents of HNE in spontaneously oxidized rat skeletal muscle, by detecting the corresponding HNE-Michael adducts in the crude biological matrix by liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Finally, we set-up and validated a sensitive, selective and specific LC-ESI-MS/MS method for the determination of HD and of the corresponding HNE-Michael adducts to monitor their profile in physiological (aging) and pathological conditions (diabetes, atherosclerosis) characterized by a carbonyl-mediated degenerative overload. The results obtained, beside to give a contribution to the understanding of the biochemical role of histidine-dipeptides, provide a strong rational to the design of novel derivatives, active as exogenous agents able to detoxify carbonyl compounds.
Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives / G. Aldini, R. Maffei Facino, G. Beretta, M. Carini. - In: BIOFACTORS. - ISSN 0951-6433. - 24:1-4(2005), pp. 77-87. ((Intervento presentato al convegno Meeting on NNE and Further Lipid Peroxidation Products : From Basic Science to Medicine tenutosi a Berlin nel 2004.
|Titolo:||Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives|
ALDINI, GIANCARLO (Corresponding)
MAFFEI FACINO, ROBERTO (Secondo)
BERETTA, GIANGIACOMO (Penultimo)
CARINI, MARINA (Ultimo)
|Parole Chiave:||carnosine; histidine-containing dipeptides; 4-hydroxy-trans-2,3nonenal; acrolein; carbonyl quencher|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/biof.5520240109|
|Appare nelle tipologie:||01 - Articolo su periodico|