title: Multifunctional 8-hydroxyquinoline-appended cyclodextrins as new inhibitors of metal-induced protein aggregation.
abstract: Mounting evidence suggests a pivotal role of metal imbalances in protein misfolding and amyloid diseases. As such, metal ions represent a promising therapeutic target. In this context, the synthesis of chelators that also contain complementary functionalities to combat the multifactorial nature of neurodegenerative diseases is a highly topical issue. We report two new 8-hydroxyquinoline-appended cyclodextrins and highlight their multifunctional properties, including their Cu(II) and Zn(II) binding abilities, and capacity to act as antioxidants and metal-induced antiaggregants. In particular, the latter property has been applied in the development of an effective assay that exploits the formation of amyloid fibrils when β-lactoglobulin A is heated in the presence of metal ions.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, 95125 Catania (Italy); Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QJ (UK).
authors.forename: Valentina
authors.initials: V
authors.lastname: Oliveri
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.forename: Antonino
authors.initials: A
authors.lastname: Puglisi
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgarlata
authors.forename: Graziella
authors.initials: G
authors.lastname: Vecchio
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000009:adverse effects / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007782:Lactoglobulins / Q000378:metabolism*; D008670:Metals / Q000009:adverse effects* / Q000737:chemistry; D015125:Oxyquinoline / Q000737:chemistry / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D015032:Zinc / Q000009:adverse effects / Q000737:chemistry
chemical_list: D000682:Amyloid; D000975:Antioxidants; D002614:Chelating Agents; D003505:Cyclodextrins; D007782:Lactoglobulins; D008670:Metals; D015125:Oxyquinoline; D003300:Copper; D015032:Zinc
keywords: antioxidants; copper; cyclodextrins; drug delivery; metal chelators; zinc