Interaction of Ferritin With Transition Metal Ions and Chelates

In this thesis, interaction of ferritin with transition metal ions and chelates is studied. First, a simple method for synthesizing gold nanoparticles stabilized by horse spleen apoferritin (HSAF) was reported using NaBH4 or 3-(N-morpholino)propanesulfonic acid (MOPS) as the reducing agent. The average particle diameters were 3.6 and 15.4 nm for NaBH4-reduced and MOPS-reduced Au-HSAF, respectively. NaBH4-reduced AuHSAF was much more effective than MOPS-reduced Au-HSAF in catalyzing the reduction of 4-nitrophenol by NaBH4, based on the greater accessibility of the NaBH4-reduced gold particle to the substrate. Methods for studying ferritin-gold nanoparticle assemblies may be readily applied to other protein-metal colloid systems. Second, the binding interactions between HSAF and three recombinant apoferritins and two commonly employed gadolinium magnetic resonance imaging (MRI) contrast agents were investigated. The anionic Gd(DTPA)2complex was undetectable in apoferritin solutions after dialysis, indicating little proteinbinding interaction. However, the non-ionic Gd(DTPA-BMA) complex bound to all apoferritins tested, producing remarkable relaxivity enhancements as well as inhibition of iron mineralization. Serum ferritin binding and dysregulation of iron mineralization may have medical significance, particularly in patients with impaired kidney function. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemistry First Advisor Ivan J. Dmochowski