Copper(II)-chelating homocarnosine glycoconjugate as a new multifunctional compound

• Homocarnosine was conjugated with trehalose through a convenient reaction.
• The chemical derivatization maintains the copper(II) affinity of homocarnosine.
• The copper(II) complex of the new conjugate has superoxide dismutase (SOD)-like activity.
• The new homocarnosine derivative inhibits the enzymatic hydrolysis of carnosine.
• The homocarnosine–trehalose conjugate delays the amyloid-β aggregation.

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.

A new multifunctional derivative of homocarnosine with trehalose has been synthesized. The copper(II) binding features of the new compound have been studied and the metal complex has superoxide dismutase (SOD)-like activity. Moreover, the conjugate inhibits the enzymatic hydrolysis of carnosine and delays the amyloid-β aggregation.Figure optionsDownload as PowerPoint slide