1. Technical Field
The present invention relates to a chelation structure, a method of forming the chelation structure, and a method of using the chelation structure to bind metal and/or heme in a mammal.
2. Related Art
Current metal chelators are beset by problems of toxicity, short vascular retention time, and high cost. These problems are exemplified by Desferal® (DFO; also commonly referred to as desferrioxamine methane sulphonate, or simply desferrioxamine) whose chemical name is N-[5-(3-[(5-aminopentyl)-hydroxycarbamoyl]-propionamido)pentyl]-3-([5-(N-hydroxyacetamido)-pentyl]-carbamoyl)-propionohydroxamic acid monomethane sulphonate). Desferal® has been used clinically since the late 1960's and remains the drug of first choice for iron chelation despite it's high cost. The therapeutic dosage of desferal® is sufficient to cause significant injury to the patient receiving the compound which can be demonstrated by growth retardation, peripheral neuropathies, and, in mice, LD50's (˜250 mg/kg) only slight above that of the typical therapeutic dosage (20-60 mg/kg) in humans. It is estimated that DFO therapy costs the typical thalassemic patient in excess of $10,000/year in US dollars.
The toxicity of current metal chelators derives, in part, from the ability of these chelator compounds to diffuse rapidly into cells and chelate essential intracellular metal (e.g., iron) stores. In the absence of these essential trace metals, the viability of the cell is adversely affected. Between the loss of the chelator into cells and their rapid clearance via the kidney, the vascular retention time of current chelators is also very poor. Again, this is readily exemplified by DFO. Upon intravascular administration, DFO undergoes complete clearance from the vasculature within approximately 20 minutes due to cellular uptake and kidney clearance.
Thus, there is a need for a metal chelator that causes less toxicity and is characterized by increased vascular retention time in comparison with current metal chelators in the prior art.