Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density.
Desferrioxamine (DFO) is a clinically approved, high affinity iron chelator used for the treatment of iron overload. Due to its short half-life and toxicity, DFO is administered for 8-12 h per day, 5-7 d per week. In this manuscript, the influence of molecular properties of hyperbranched polyglycerol (HPG)-DFO conjugates on their iron binding by isothermal titration calorimetry, iron removal efficiency from ferritin in presence and absence of a low molecular weight (MW) iron chelator, and protection against iron mediated oxidation of proteins is reported. The iron binding properties of HPG-DFO are slightly altered with size and DFO density of conjugates. The lower MW conjugate shows greater iron removal efficiency at room temperature, however, the efficacy of high MW conjugates increases at physiological temperature. The iron removal from ferritin by HPG-DFO conjugates increases significantly in presence of a low MW chelator, suggesting the potential of combination therapy. The molecular properties of the polymer scaffold also have influence on the prevention of iron mediated oxidation of proteins by the conjugates. The results therefore help to define the iron binding thermodynamics of HPG-DFO and their dependence on MW, and can be extended to improve the general understanding of polymeric chelator-iron interactions in situ.
Centre for Blood Research, Department of Pathology and Laboratory MedicineThe University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Jasmine L
JL
Hamilton
Centre for Blood Research, Department of Pathology and Laboratory MedicineThe University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Muhammad Imran
MI
Ul-Haq
Michael Smith Laboratories, Department of Chemical and Biological EngineeringThe University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
A Louise
AL
Creagh
Michael Smith Laboratories, Department of Chemical and Biological EngineeringThe University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Charles A
CA
Haynes
Centre for Blood Research, Department of Pathology and Laboratory MedicineThe University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.|Department of Chemistry, Life Sciences Centre, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Jayachandran N
JN
Kizhakkedathu
D003676:Deferoxamine / Q000737:chemistry* / Q000627:therapeutic use; D005990:Glycerol / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000737:chemistry*; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry
D007502:Iron Chelating Agents; D011108:Polymers; C043941:polyglycerol; D007501:Iron; D003676:Deferoxamine; D005990:Glycerol
desferrioxamine; hyperbranched polyglycerol; iron chelators; iron overload; macromolecular therapeutics