l-Carnosine (beta-Ala-l-His) and several other histidine-containing peptides, including two N-methylated forms on the imidazole ring (l-anserine and l-balenine), two derivatives modified on the carboxyl function (carcinine and l-carnosinamide), two analogues differing in the length of the N-terminal residue (l-homocarnosine and Gly-l-His) and the N-acetyl derivatives, were investigated as activators of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 18.104.22.168). The four human isoforms hCA I, II, VA and IX were activated in the low to high micromolar range, with a rather complex structure activity relationship. A performed computational study allowed us to rationalize these results and to propose a binding mode of these activators within the enzyme active site. Similarly to other CA activators, the here studied peptides could find relevant pharmacological applications such as in the management of CA deficiencies, for therapy memory and enhancing cognition or for artificial tissues engineering.
Activation Effects of Carnosine- and Histidine-Containing Dipeptides on Human Carbonic Anhydrases: A Comprehensive Study / G. Vistoli, G. Aldini, L. Fumagalli, C. Dallanoce, A. Angeli, C.T. Supuran. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:5(2020 Mar 01).
|Titolo:||Activation Effects of Carnosine- and Histidine-Containing Dipeptides on Human Carbonic Anhydrases: A Comprehensive Study|
VISTOLI, GIULIO (Primo) [Conceptualization] (Corresponding)
ALDINI, GIANCARLO (Secondo) [Methodology]
FUMAGALLI, LAURA [Investigation]
DALLANOCE, CLELIA MARIANGIOLA LUISA [Investigation]
|Parole Chiave:||carbonic anhydrase; activator; proton shuttling; carnosine; histidine; dipeptide;|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||1-mar-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/ijms21051761|
|Appare nelle tipologie:||01 - Articolo su periodico|