Copper Exchange and Redox Activity of a Prototypical 8-Hydroxyquinoline: Implications for Therapeutic Chelation.
Inorg Chem
; 55(15): 7317-9, 2016 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-27409140
ABSTRACT
The N-truncated ß-amyloid (Aß) isoform Aß4-x is known to bind Cu(2+) via a redox-silent ATCUN motif with a conditional Kd = 30 fM at pH 7.4. This study characterizes the Cu(2+) interactions and redox activity of Aßx-16 (x = 1, 4) and 2-[(dimethylamino)-methyl-8-hydroxyquinoline, a terdentate 8-hydroxyquinoline (8HQ) with a conditional Kd(CuL) = 35 pM at pH 7.4. Metal transfer between Cu(Aß1-16), CuL, CuL2, and ternary CuL(NIm(Aß)) was rapid, while the corresponding equilibrium between L and Aß4-16 occurred slowly via a metastable CuL(NIm(Aß)) intermediate. Both CuL and CuL2 were redox-silent in the presence of ascorbate, but a CuL(NIm) complex can generate reactive oxygen species. Because the NIm(Aß) ligand will be readily exchangeable with NIm ligands of ubiquitous protein His side chains in vivo, this class of 8HQ ligand could transfer Cu(2+) from inert Cu(Aß4-x) to redox-active CuL(NIm). These findings have implications for the use of terdentate 8HQs as therapeutic chelators to treat neurodegenerative disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Peptídeos beta-Amiloides
/
Oxiquinolina
/
Cobre
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article