title: Carbonic anhydrase activators: gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced activatory effects on several mammalian isoforms.
abstract: Lipoic acid moieties were attached to amine or amino acids showing activating properties against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The obtained lipoic acid conjugates of histamine, L-histidine methyl ester, and L-carnosine methyl ester were attached to gold nanoparticles (NPs) by reaction with Au(III) salts in reducing conditions. The CA activators (CAAs)-coated NPs showed low nanomolar activation (K(A)s of 1-9 nM) of relevant cytosolic, membrane-bound, mitochondrial, and transmembrane CA isoforms, such as CA I, II, IV, VA, VII, and XIV. These NPs also effectively activated CAs ex vivo, in whole blood experiments, with an increase of 200-280% of the CA activity. This is the first example of enzyme activation with nanoparticles and may lead to biomedical applications for conditions in which the CA activity is diminished, such as aging, Alzheimer's disease, or CA deficiency syndrome.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors.forename: Mohamed-Chiheb
authors.initials: MC
authors.lastname: Saada
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montero
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002256:Carbonic Anhydrases / Q000097:blood / Q000737:chemistry*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D020536:Enzyme Activators / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006046:Gold; D006632:Histamine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000097:blood / Q000737:chemistry; D053768:Metal Nanoparticles; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020536:Enzyme Activators; D007527:Isoenzymes; D011994:Recombinant Proteins; D006639:Histidine; D008063:Thioctic Acid; D006046:Gold; D006632:Histamine; D002336:Carnosine; C053861:histidine methyl ester; D002256:Carbonic Anhydrases