Copper and rheumatoid arthritis - an in vitro study of metal-protein interactions

• Main Author: Singh, Manooj
• Other Authors: Jackson, Graham Ellis
• Format: Dissertation
• Language: English
• Published: University of Cape Town 2014
• Subjects: Chemistry
• Online Access: http://hdl.handle.net/11427/9604

Includes bibliographical references. === Acute and Chronic inflammations in Rheumatoid Arthritis are characterized by, among other features, changes in the metabolism of copper. Previous studies have shown that administration of exogenous copper, and the in vivo manipulation of endogenous copper may provide new ways of coping with the problem of anti-inflammatory/anti-arthritic therapies. Computer models of blood plasma have attempted to rationalize the use of copper complexes in this regard. This thesis describes the design and commissioning of an ultrafiltration apparatus to study metal interactions with blood proteins. The results are compared with equilibrium dialysis. The systems studied using this technique includes, the binding of Cu(ll) to HSA and BSA, ternary Cu(ll)-HSA-amino acid systems, as well as competitive studies of the Cu(ll)-HSA system with Mg(ll), Ca(ll) and Zn(ll). The ultrafiltrate was analysed using HPLC and atomic absorption spectroscopy. Protein preparation was found to be important and the different methods used for protein purification were compared using gel electrophoresis and atomic absorption. Binding studies of chelating agents as well as several pharmaceuticals in human blood serum were carried out and compared with computer modelling studies.