Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein toxicity

Eur J Med Chem. 2017 Jul 28:135:447-457. doi: 10.1016/j.ejmech.2017.04.060. Epub 2017 Apr 24.

Abstract

Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated.

Keywords: Antiglycating effect; Aβ aggregation; Carnosine; Copper complexes; Trehalose.

MeSH terms

  • Acrolein / antagonists & inhibitors*
  • Acrolein / toxicity
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Carnosine / chemistry
  • Carnosine / pharmacology*
  • Copper / chemistry
  • Copper / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Protein Aggregates / drug effects
  • Structure-Activity Relationship
  • Trehalose / chemistry
  • Trehalose / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Organometallic Compounds
  • Protein Aggregates
  • Acrolein
  • Copper
  • Carnosine
  • Trehalose