Copper(II)-chelating homocarnosine glycoconjugate as a new multifunctional compound.
Homocarnosine is an endogenous dipeptide distributed in cerebral regions and cerebrospinal fluid. Homocarnosine may serve as an antioxidant, free radical scavenger, neurotransmitter, buffering system and metal chelating agent, especially for copper(II) and zinc(II). The homeostasis of homocarnosine is regulated by carnosinases; the serum-circulating isoform of these metallodipeptidases partially hydrolyses homocarnosine in the blood. The enzyme activity is also inhibited by homocarnosine itself in a dose-dependent manner. We synthesized a new multifunctional homocarnosine derivative with trehalose, a disaccharide that possesses several beneficial properties, among which the inhibition of protein aggregation (i.e. Aβ amyloid and polyglutamine proteins) involved in widespread neurodegenerative disorders. We studied the copper(II) binding features of the new conjugate by means of potentiometric and spectroscopic techniques (UV-visible and circular dichroism) and the superoxide dismutase-like activity of the copper(II) complexes with homocarnosine and its trehalose conjugate was evaluated. The inhibitory effect of the new homocarnosine derivative on the carnosinase activity and its effects on Aβ aggregation were also investigated.
Institute of Biostructure and Bioimaging, National Research Council (CNR), Viale A. Doria 6, Catania, Italy.
Giuseppa I
GI
Grasso
Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania, Italy.
Giuseppe
G
Arena
Institute of Biostructure and Bioimaging, National Research Council (CNR), Viale A. Doria 6, Catania, Italy. Electronic address: fbellia@unict.it.
Francesco
F
Bellia
Institute of Biostructure and Bioimaging, National Research Council (CNR), Viale A. Doria 6, Catania, Italy; Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania, Italy.
Enrico
E
Rizzarelli
Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania, Italy.
Graziella
G
Vecchio
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D006001:Glycoconjugates / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000378:metabolism; D014199:Trehalose / Q000737:chemistry
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D056831:Coordination Complexes; D006001:Glycoconjugates; C005038:homocarnosine; D003300:Copper; D002336:Carnosine; D014199:Trehalose; D013482:Superoxide Dismutase
Amyloid; Carnosinase; Copper; Dipeptide; Superoxide dismutase mimics; Trehalose