Issue 21, 2012

Chelation therapy in Wilson's disease: from d-penicillamine to the design of selective bioinspired intracellular Cu(i) chelators

Abstract

Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.

Graphical abstract: Chelation therapy in Wilson's disease: from d-penicillamine to the design of selective bioinspired intracellular Cu(i) chelators

Article information

Article type
Perspective
Submitted
15 Nov 2011
Accepted
12 Jan 2012
First published
13 Feb 2012

Dalton Trans., 2012,41, 6359-6370

Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators

P. Delangle and E. Mintz, Dalton Trans., 2012, 41, 6359 DOI: 10.1039/C2DT12188C

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