An Equation for Predicting Binding Strengths of Metal Cations to Protein of Human Serum Transferrin

Because human serum transferrin (hTF) exists freely in serum, it is a potential target for cancer treatment drugs and in curing iron-overloaded conditions in patients via long-term transfusion therapy. The understanding of the interactions between hTF and metal ions is very important for biological, pharmalogical, toxicological, and other protein engineering purposes. In this paper, a simple linear free energy correlation is proposed to predict the binding strength between hTF protein and metal cations. The stability constants (KML) for a family of metal—hTF complexes can be correlated to the non-solvation energies (Gn, Mn+) and the radii (rMn+) of cations by equation: 2.303RTlogKML = -a*ML Gn, Mn+ b**ML *ML rMn+ + Gf, Mn+, where the coefficients a*ML, b**ML, and *ML characterize a particular family of metal-protein complexes. The binding strength is determined by both the physical properties (charge and size or ionic radius, rMn+) and chemical properties (non-